Institut für Biologie

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3D chromatin maps of a brown alga reveal U/V sex chromosome spatial organization
(2024) Liu, Pengfei; Vigneau, Jeromine; Craig, Rory J.; Barrera-Redondo, Josué; Avdievich, Elena; Martinho, Claudia; Borg, Michael; Haas, Fabian B.; Liu, Chang; Coelho, Susana M.
Nuclear three dimensional (3D) folding of chromatin structure has been linked to gene expression regulation and correct developmental programs, but little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their role in sex determination. Here, we determine the sex-specific 3D organization of the model brown alga Ectocarpus chromosomes at 2 kb resolution, by mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report that Ectocarpus interphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotransposons. The Ectocarpus chromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone proteins. We show that the sex determining region (SDR) within the U and V chromosomes are insulated and span the centromeres and we link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of the U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element, providing insights regarding the impact of a latent giant dsDNA virus on the host genome’s 3D chromosomal folding.
Comparison of whole genomes of tick-borne encephalitis virus from mountainous alpine regions and regions with a lower altitude
(2021) Lemhöfer, G.; Chitimia-Dobler, L.; Dobler, G.; Bestehorn-Willmann, Malena
Tick-borne encephalitis (TBE) has been a notifiable disease in Germany since 2001. Its causative agent, the TBE virus (TBEV), is the most important arbovirus in Europe and Northern Asia. The illness, caused by the European Subtype usually displays flu-like symptoms, but can result in sequelae and, in 2 % of all cases, in death. Over the last few decades, the virus has spread into new habitats, such as higher altitudes in the Alpine region. For this study, it was hypothesized that the environmental challenges that the virus might be exposed to at such altitudes could lead to the selection of viral strains with a higher resilience to such environmental factors. To determine whether strains identified at higher altitudes possessed different genetic traits compared to viruses from lower altitudes, an analysis of viral genomes from higher Alpine altitudes (> 500 m above sea level) (n = 5) and lower altitudes (< 500 m above sea level) (n = 4) was performed. No common phylogenetic ancestry or shared amino acid substitutions could be identified that differentiated the alpine from the lowland viral strains. These findings support the idea of many individual introductions of TBEV into the alpine region and the establishment of foci due to non-viral specific factors such as favorable conditions for vector species and host animals due to climate change.
Decoding the geography of natural TBEV microfoci in German: a geostatistical approach based on land-use patterns and climatological conditions
(2022) Borde, Johannes P.; Glaser, Rüdiger; Braun, Klaus; Riach, Nils; Hologa, Rafael; Kaier, Klaus; Chitimia-Dobler, Lidia; Dobler, Gerhard
Background: Tickborne-encephalitis (TBE) is a potentially life-threating neurological disease that is mainly transmitted by ticks. The goal of the present study is to analyze the potential uniform environmental patterns of the identified TBEV microfoci in Germany. The results are used to calculate probabilities for the present distribution of TBEV microfoci in Germany based on a geostatistical model. Methods: We aim to consider the specification of environmental characteristics of locations of TBEV microfoci detected in Germany using open access epidemiological, geographical and climatological data sources. We use a two-step geostatistical approach, where in a first step, the characteristics of a broad set of environmental variables between the 56 TBEV microfoci and a control or comparator set of 3575 sampling points covering Germany are compared using Fisher’s Exact Test. In the second step, we select the most important variables, which are then used in a MaxEnt distribution model to calculate a high resolution (400 × 400 m) probability map for the presence of TBEV covering the entire area of Germany. Results: The findings from the MaxEnt prediction model indicate that multi annual actual evapotranspiration (27.0%) and multi annual hot days (22.5%) have the highest contribution to our model. These two variables are followed by four additional variables with a lower, but still important, explanatory influence: Land cover classes (19.6%), multi annual minimum air temperature (14.9%), multi annual sunshine duration (9.0%), and distance to coniferous and mixed forest border (7.0%). Conclusions: Our findings are based on defined TBEV microfoci with known histories of infection and the repeated confirmation of the virus in the last years, resulting in an in-depth high-resolution model/map of TBEV microfoci in Germany. Multi annual actual evapotranspiration (27%) and multi annual hot days (22.5%) have the most explanatory power in our model. The results may be used to tailor specific regional preventive measures and investigations.
Development and validation of a novel enzyme-linked immunosorbent assay for the differentiation of tick-borne encephalitis infections caused by different virus subtypes
(2025) Freimane, Zane; Dobler, Gerhard; Chitimia-Dobler, Lidia; Karelis, Guntis; Girl, Philipp; Kuzmane, Sanita; Savicka, Oksana; Erber, Wilhelm; Zavadska, Dace
Objectives: Tick-borne encephalitis (TBE) is an infection caused by the tick-borne encephalitis virus (TBEV) that can lead to symptoms of central nervous system inflammation. There are five subtypes of TBEV, three of which – European, Siberian and Far Eastern – occur in Europe. As it is thought that different subtype infections exhibit varying clinical courses and outcomes, serological differentiation of the virus subtypes is clearly important. However, to date, this has proved difficult to achieve. Methods: An ELISA format was developed based on TBE virus NS1 antigen against the European, Siberian and Far Eastern subtype. The three NS1 antigens were biotechnologically produced in a human cell line and used for ELISA coating. Sera from German (European subtype) and Russian (Siberian and/or Far Eastern subtypes) TBE patients with positive TBEV IgG were used to test the reactivity against these three NS1 antigens. Results: Testing of 23 German and 32 Russian TBEV IgG-positive sera showed that the ELISA was able to differentiate between TBEV European subtype and TBEV Siberian and Far Eastern subtype infections. Conclusions: In geographical areas where two or more TBEV subtype infections can occur, the NS1-IgG ELISA developed here constitutes an important diagnostic tool to differentiate between European subtype infections and Siberian/Far Eastern subtype infections and to use the new assay for epidemiological studies to clarify the importance of particular subtype infections in an area. Consequently, it may help to better describe and anticipate the clinical courses and outcomes of particular TBEV subtype infections.
Echinococcus multilocularis and other taeniid metacestodes of muskrats in Luxembourg: prevalence, risk factors, parasite reproduction, and genetic diversity
(2022) Martini, Matilde; Dumendiak, Sonja; Gagliardo, Anna; Ragazzini, Francesco; La Rosa, Letizia; Giunchi, Dimitri; Thielen, Frank; Romig, Thomas; Massolo, Alessandro; Wassermann, Marion
Muskrats (Ondatra zibethicus) are competent intermediate hosts for Echinococcus multilocularis, are frequently infected with this zoonotic cestode, and have even been proposed as a target species to monitor endemicity levels of this parasite. However, their contribution to maintaining the parasitic lifecycle is still unclear. To obtain data on infection frequency and reproductive potential, 280 muskrats from the Grand Duchy of Luxembourg were examined for cestode larvae in the years 2013–2017. Based on morphological and molecular identification, Echinococcus multilocularis was found at a prevalence of 14.6%. Other metacestodes were Hydatigera kamiyai, with a prevalence of 45.7%, Taenia martis with 8.9%, Taenia polyacantha with 5.0%, and Versteria mustelae, which was found in 0.7% of all muskrats. More than 80% of E. multilocularis-infected muskrats contained fertile metacestodes with a mean number of >300,000 (and up to 1,609,816) protoscoleces, which is by far the highest reproductive potential known from any intermediate host species in Europe. Temporal analysis of E. multilocularis prevalence within the study period (and in comparison with earlier data) strongly indicates a robust increase in the studied area. Host age seemed to be an important risk factor for infection, as well as co-infections with Hydatigera kamiyai. A preference for the right medial lobe of the liver as the location of E. multilocularis metacestode was observed. Intraspecific genetic variation among 89 discrete E. multilocularis metacestodes was non-existent based on 300–1590 bp sections of cox1. This is a stark contrast to H. kamiyai, of which nine haplotypes were found on a short 318 bp section of cox1, resulting in genetic diversity in the small country of Luxembourg at a similar level than previously reported from large stretches of Europe and northern Asia.
Echinococcus multilocularis and other zoonotic helminths in red foxes (Vulpes vulpes) from a southern German hotspot for human alveolar echinococcosis
(2023) Schneider, Carina; Kratzer, Wolfgang; Binzberger, Andreas; Schlingeloff, Patrycja; Baumann, Sven; Romig, Thomas; Schmidberger, Julian
Background: We describe the spatial distribution of Echinococcus multilocularis in its main definitive host, the red fox, and the distribution of human cases of alveolar echinococcosis (AE) within a highly endemic focus in southern Germany (13.7–19.9/100,000 in 1992–2018). Human cases were unequally distributed within the endemicity focus. The purpose of the study was to test whether this is reflected in the small-scale distribution of E. multilocularis in foxes. Methods: Three areas with contrasting numbers of human cases were selected within the counties of Ravensburg and Alb-Donau, Baden-Württemberg, Germany. From 2018 to 2020, a total of 240 fox carcasses were obtained from traditional hunters in these areas. Carcasses were necropsied and examined for the presence of intestinal helminths. The statistical analysis was performed with SAS version 9.4, and the geo-mapping with QGIS version 3.16.0 Hannover. Results: The prevalence of E. multilocularis in foxes was 44/106 (41.5%) in area I (commune Leutkirch and environs), 30/59 (50.8%) in area II (commune Isny and environs), and 31/75 (41.3%) in area III (commune Ehingen and environs). From 1992 to 2018, a total of nine human cases of alveolar echinococcosis were recorded in area I, five cases were recorded in study area III, and no cases were recorded in area II. No statistically significant differences between the areas were observed ( P > 0.05) for intestinal infections with E. multilocularis , and no apparent spatial correlation with the small-scale distribution of human cases was found. Concerning other zoonotic helminths, Toxocara spp. were equally common, with prevalence of 38.7%, 47.4% and 48.0%, respectively, while the frequency of Alaria alata varied among the study areas (0.0–9.4%), probably reflecting the specific habitat requirements for the establishment of its complex life cycle. Conclusions: Echinococcus multilocularis is highly prevalent in foxes in all the studied areas. The varying number of human AE cases within these areas should therefore be caused by factors other than the intensity of parasite transmission in foxes.
Environmental contamination with feces of free-roaming dogs and the risk of transmission of Echinococcus and Taenia species in urban regions of southeastern Iran
(2024) Shamsaddini, Saeedeh; Schneider, Carina; Dumendiak, Sonja; Aghassi, Hossein; Kamyabi, Hossein; Akhlaghi, Elham; Wassermann, Marion; Fasihi Harandi, Majid; Deplazes, Peter; Romig, Thomas
Background: Dogs are the most important definitive hosts of zoonotic taeniid helminths worldwide. Different Echinococcus and Taenia species of domestic and wild carnivores pose a potential risk to human population. High populations of free-roaming dogs (FRDs) in urban areas of Iran and widespread contamination of the environment with dog feces is a potential source of infecting people living in the urban regions with cystic echinococcosis (CE). Our knowledge on the risk of CE transmission in the urban settings in the endemic regions is limited. The present study surveyed the species and genotypes of E. granulosus sensu lato and other taeniids by examining feces of free-roaming dogs in the urban areas in the city of Kerman, southeastern Iran. Methods: The city was divided into 100 consecutive blocks of which 25 blocks were randomly selected. Fecal samples of FRDs were counted, mapped and fresh samples were collected. Then Zinc chloride flotation, and sequential sieving was performed, and the samples were examined under an inverted microscope. Single individual taeniid eggs were isolated, partial nad1 gene was amplified and sequenced to identify species and genotypes. Results: In total 5607 fecal samples of dogs were mapped and 83 fresh samples were collected. Taeniid eggs were detected in nine fecal samples (10.8%) from seven out of the 25 city blocks (28.0%). Echinococcus eggs were found in four samples (4.8%) from three city blocks, two samples containing E. granulosus sensu stricto (2.4%), two samples containing E. canadensis G6/7 (2.4%). In addition, three samples contained eggs of Taenia hydatigena (3.6%), and one sample of Taenia serialis (1.2%). Conclusions: This study documented the potential risk of CE transmission to humans resulting from the feces of dogs roaming freely in urban areas.
EvaMol : A python tool for evaluating molecules in hit-to-lead optimization
(2025) Herzog, Anna-Maria; Steuber, Julia; Fritz, Günter
This Python script was developed as a tool in structure-based drug discovery processes, such as fragment-to-lead-optimization, where a large number of variants of an initially identified hit molecule have to be evaluated and ranked in silico. The tool facilitates the identification and selection of follow-up drug candidates with improved predicted pharmacokinetic and binding properties. These candidates can derive from different procedures like similarity search or systematic chemical modifications. The initial hit data are provided either as coordinates of the protein-molecule complex obtained experimentally or by in silico methods such as docking making the script a versatile tool adaptable to variable workflows.
Exploring ND-011992, a quinazoline-type inhibitor targeting quinone reductases and quinol oxidases
(2023) Kägi, Jan; Sloan, Willough; Schimpf, Johannes; Nasiri, Hamid R.; Lashley, Dana; Friedrich, Thorsten
Bacterial energy metabolism has become a promising target for next-generation tuberculosis chemotherapy. One strategy to hamper ATP production is to inhibit the respiratory oxidases. The respiratory chain of Mycobacterium tuberculosis comprises a cytochrome bcc:aa3 and a cytochrome bd ubiquinol oxidase that require a combined approach to block their activity. A quinazoline-type compound called ND-011992 has previously been reported to ineffectively inhibit bd oxidases, but to act bactericidal in combination with inhibitors of cytochrome bcc:aa3 oxidase. Due to the structural similarity of ND-011992 to quinazoline-type inhibitors of respiratory complex I, we suspected that this compound is also capable of blocking other respiratory chain complexes. Here, we synthesized ND-011992 and a bromine derivative to study their effect on the respiratory chain complexes of Escherichia coli. And indeed, ND-011992 was found to inhibit respiratory complex I and bo3 oxidase in addition to bd-I and bd-II oxidases. The IC50 values are all in the low micromolar range, with inhibition of complex I providing the lowest value with an IC50 of 0.12 µM. Thus, ND-011992 acts on both, quinone reductases and quinol oxidases and could be very well suited to regulate the activity of the entire respiratory chain.
From import to establishment? Experimental evidence for seasonal outdoor survival of two Rhipicephalus species in Germany
(2025) Fachet-Lehmann, Katrin; Lindau, Alexander; Mackenstedt, Ute
The brown dog tick (Rhipicephalus sanguineus s.l.), though not endemic in Germany, is regularly introduced via travelers with dogs and imported rescue dogs. Due to its relevance in veterinary and human medicine, its potential to establish in Germany’s climate is of interest. Although previous studies confirm indoor survival and reproduction of R. sanguineus s.s. in Germany, climate change and milder winters may also allow outdoor survival. This study assessed the survival of R. sanguineus s.s. and R. innaei from February 2023 to May 2024 using laboratory-bred ticks placed at indoor and outdoor sites. Tick survival (adults, nymphs, larvae) was monitored weekly, along with temperature and humidity. Reproductive success was evaluated via oviposition and larval hatching. R. sanguineus s.s. adults survived up to 44 weeks, nymphs up to 20 weeks, and larvae up to 5 weeks. R. innaei showed shorter survival (37, 10, and 4 weeks, respectively). Successful oviposition and larval hatching occurred outdoors between May´23 and September´23 for both species. However, winter survival was not observed; all ticks died following sub-zero temperatures in December´23. Despite the inability to overwinter outdoors, both species can survive for extended periods in spring and summer and may enter homes via dogs, where conditions favor year-round survival. Their ability to transition indoors via dogs, where conditions favor year-round survival, suggests a potential for establishment in Germany through combined indoor and seasonal outdoor persistence.
Functionality of the Na+-translocating NADH:quinone oxidoreductase and quinol:fumarate reductase from Prevotella bryantii inferred from homology modeling
(2024) Hau, Jann-Louis; Schleicher, Lena; Herdan, Sebastian; Simon, Jörg; Seifert, Jana; Fritz, Günter; Steuber, Julia
Members of the family Prevotellaceae are Gram-negative, obligate anaerobic bacteria found in animal and human microbiota. In Prevotella bryantii , the Na + -translocating NADH:quinone oxidoreductase (NQR) and quinol:fumarate reductase (QFR) interact using menaquinone as electron carrier, catalyzing NADH:fumarate oxidoreduction. P. bryantii NQR establishes a sodium-motive force, whereas P. bryantii QFR does not contribute to membrane energization. To elucidate the possible mode of function, we present 3D structural models of NQR and QFR from P. bryantii to predict cofactor-binding sites, electron transfer routes and interaction with substrates. Molecular docking reveals the proposed mode of menaquinone binding to the quinone site of subunit NqrB of P. bryantii NQR. A comparison of the 3D model of P. bryantii QFR with experimentally determined structures suggests alternative pathways for transmembrane proton transport in this type of QFR . Our findings are relevant for NADH-dependent succinate formation in anaerobic bacteria which operate both NQR and QFR.
Hitze als Schlüssel zur Aufklärung der Lysogenie beim SPß-Phagen
(2025) Kohm, Katharina
Identification of novel genes including NAV2 associated with isolated tall stature
(2023) Weiss, Birgit; Ott, Tim; Vick, Philipp; Lui, Julian C.; Roeth, Ralph; Vogel, Sebastian; Waldmüller, Stephan; Hoffmann, Sandra; Baron, Jeffrey; Wit, Jan M.; Rappold, Gudrun A.
Very tall people attract much attention and represent a clinically and genetically heterogenous group of individuals. Identifying the genetic etiology can provide important insights into the molecular mechanisms regulating linear growth. We studied a three-generation pedigree with five isolated (non-syndromic) tall members and one individual with normal stature by whole exome sequencing; the tallest man had a height of 211 cm. Six heterozygous gene variants predicted as damaging were shared among the four genetically related tall individuals and not present in a family member with normal height. To gain insight into the putative role of these candidate genes in bone growth, we assessed the transcriptome of murine growth plate by microarray and RNA Seq. Two (Ift140, Nav2) of the six genes were well-expressed in the growth plate. Nav2 (p-value 1.91E-62) as well as Ift140 (p-value of 2.98E-06) showed significant downregulation of gene expression between the proliferative and hypertrophic zone, suggesting that these genes may be involved in the regulation of chondrocyte proliferation and/or hypertrophic differentiation. IFT140, NAV2 and SCAF11 have also significantly associated with height in GWAS studies. Pathway and network analysis indicated functional connections between IFT140, NAV2 and SCAF11 and previously associated (tall) stature genes. Knockout of the all-trans retinoic acid responsive gene, neuron navigator 2 NAV2, in Xenopus supports its functional role as a growth promotor. Collectively, our data expand the spectrum of genes with a putative role in tall stature phenotypes and, among other genes, highlight NAV2 as an interesting gene to this phenotype.
Mitochondrial genome amplification of avian haemosporidian parasites from single-infected wildlife samples using a novel nested PCR approach
(2023) Musa, Sandrine
Haemosporidian parasites that infect birds (Apicomplexa: Haemosporida) are blood parasites that require an invertebrate host (vector) and a vertebrate host for their lifecycle and cause malaria-like diseases. This group of parasites has provided valuable insights into host specificity, virulence, and parasite dispersal. Additionally, they have played a significant role in reshaping our understanding of the evolutionary history of apicomplexans. In order to accurately identify species and to address phylogenetic questions such as the timing of the haemosporidian radiation, the use of a sufficiently large genetic data set is crucial. However, acquiring this genetic data poses significant challenges. In this research, a sensitive nested PCR assay was developed. This assay allows for the easy amplification of complete mitochondrial genomes of haemosporidian parasites in birds, even during the chronic stage of infection. The effectiveness of this new nested PCR assay was evaluated using blood and tissue samples of birds with verified single parasite infections from previous studies. The approach involves amplifying four overlapping fragments of the mitochondrial genome and requires DNA extracts from single-infected samples. This method successfully amplified the complete mitochondrial genomes of 24 distinct haemosporidian parasite lineages found in various bird species. This data is invaluable for conducting phylogenetic analyses and accurately defining species. Furthermore, this study proposes the existence of at least 15 new haemosporidian parasite species based on the genetic information obtained. Data regarding pGRW04, previously categorized as Plasmodium relictum like pSGS1 and pGRW11, indicates that the pGRW04 lineage is actually a separate, hidden Plasmodium species.
MMP21 behaves as a fluid flow transported morphogen to impart laterality during development
(2025) Ott, Tim; Brugger, Amelie; Szenker-Ravi, Emmanuelle; Kurrle, Yvonne; Aberle, Olivia; Tisler, Matthias; Blum, Martin; Whalen, Sandra; Bouvagnet, Patrice; Reversade, Bruno; Schweickert, Axel
Heterotaxy (HTX) is frequently caused by deleterious variants in the gene encoding Matrix metallopeptidase 21 (MMP21). However, the underlying pathomechanism has not been ascertained. In this study, we report on a novel HTX-associated MMP21 knockout allele in humans and investigate the peptidase’s role during laterality development using Xenopus embryos as animal model. The targeted inactivation of mmp21 in f0 mutant Xenopus successfully phenocopied the human HTX condition, yet the cilia-driven leftward fluid flow, which initiates asymmetric gene activity at the left-right organizer (LRO), was unaltered in mmp21 null frogs. Instead, our analysis of downstream events revealed that flow response, the left-sided repression of dand5, could not take place. Remarkably, gain-of-function experiments demonstrated that Mmp21 spreads over LRO cells and triggers flow response. Additionally, Mmp21 functions upstream of Cirop, another metallopeptidase, which we found specifically localized to LRO cilia. Thus, our findings suggest that Mmp21 may be the long-sought morphogen, which is actively transported by the leftward fluid flow to Cirop-laden cilia, in order to specify the left side of the embryo.
Molecular communication of the membrane insertase YidC with translocase SecYEG affects client proteins
(2021) Steudle, Anja; Spann, Dirk; Pross, Eva; Shanmugam, Sri Karthika; Dalbey, Ross E.; Kuhn, Andreas
The membrane insertase YidC inserts newly synthesized proteins by its hydrophobic slide consisting of the two transmembrane (TM) segments TM3 and TM5. Mutations in this part of the protein affect the insertion of the client proteins. We show here that a quintuple mutation, termed YidC-5S, inhibits the insertion of the subunit a of the FoF1 ATP synthase but has no effect on the insertion of the Sec-independent M13 procoat protein and the C-tail protein SciP. Further investigations show that the interaction of YidC-5S with SecY is inhibited. The purified and fluorescently labeled YidC-5S did not approach SecYEG when both were co-reconstituted in proteoliposomes in contrast to the co-reconstituted YidC wild type. These results suggest that TM3 and TM5 are involved in the formation of a common YidC-SecYEG complex that is required for the insertion of Sec/YidC-dependent client proteins.
Molting incidents of Hyalomma spp. carrying human pathogens in Germany under different weather conditions
(2024) Chitimia-Dobler, Lidia; Springer, Andrea; Lang, Daniel; Lindau, Alexander; Fachet, Katrin; Dobler, Gerhard; Nijhof, Ard M.; Strube, Christina; Mackenstedt, Ute
Background: Hyalomma marginatum and H. rufipes are two-host tick species, which are mainly distributed in southern Europe, Africa to central Asia but may also be found in Central and Northern Europe through introduction by migratory birds. Methods: Ticks were collected while feeding or crawling on animals and humans, or from the environment, in different regions in Germany, between 2019 and 2021 in a citizen science study and from 2022 to 2023 in the wake of this study. Results: From 2019 to 2023, a total of 212 Hyalomma adult ticks were detected in Germany. This included 132 H. marginatum and 43 H. rufipes ticks sent to research institutions and 37 photographic records that were only identified to genus level. The number of detected ticks varied over the years, with the highest number of 119 specimens recorded in 2019, followed by 57 in 2020. Most of the specimens were collected from horses, while some were collected from other animals, humans or found crawling on human clothes or other objects inside or outside houses. The screening of 175 specimens for Crimean-Congo hemorrhagic fever virus and of 132 specimens for Babesia/Theileria spp. by PCR gave negative results, while human-pathogenic Rickettsia were detected in 44% (77/175) of the total samples. Subsequent amplicon sequencing and phylogenetic analysis of representative samples determined the species of 41 Rickettsia aeschlimannii and one R. slovaca sequences. Conclusions: Analysis of climatic factors indicated a significantly higher probability of Hyalomma occurrence at locations with higher average spring temperature during the years 2019 and 2020 compared to randomly generated pseudo-absence locations. Dry and hot conditions probably facilitated Hyalomma nymphs’ survival and molting into adults during these yea
Morphological and molecular identification of sarcocystis arctica in captive cheetahs (Acinonyx jubatus) in China helps clarify phylogenetic relationships with Sarcocystis caninum and Sarcocystis felis
(2025) Liao, Zhe; Zhu, Niuping; Yang, Yurong; Deng, Shuangsheng; Jäkel, Thomas; Hu, Junjie; Salvarani, Felipe M.; Domingues, Sheyla Farhayldes Souza; Da Silveira, Júlia Angélica Gonçalves
To date, only one case is known where protozoan parasites of the genus Sarcocystis were found to infect cheetahs ( Acinonyx jubatus ); the cysts in the musculature were morphologically identified as S. felis . Here, we characterized sarcocysts by morphological and molecular methods that were observed in cheetahs who died in zoos in China. Only one type of sarcocyst was present in two of six cheetahs. By light microscopy, the sarcocyst wall was striated, 1.4–2.1 μm thick. Ultrastructurally, the wall had irregular-shaped, small villar protrusions, resembling wall type 9c, similar to those of S. arctica , S. caninum , and S. felis . The samples shared their highest molecular identity values with those of S. arctica and S. caninum : 99.9–100% and 99.8–100% (18S rRNA), 99.5% and 99.3–99.5% (28S rRNA), 95.9–97.5% and 96.3–97.3% (ITS-1), and 99.6% and 99.2–99.7% ( cox 1), respectively. Compared with ITS-1 of S. felis , identities ranged between 87.5% and 88.9%. Phylogenetic reconstruction revealed that the newly sequenced Sarcocystis clustered with S. arctica and S. caninum , whereas S. felis (ITS-1) and S. canis (ITS-1, 18S rRNA, cox 1) were sister species. Thus, we addressed the Sarcocystis species from the cheetahs as S. arctica , which is the first record of a Sarcocystis species believed to be specific for canids as intermediate hosts to infect a feline host.
Myostatin regulates the production of fibroblast growth factor 23 (FGF23) in UMR106 osteoblast–like cells
(2021) Ewendt, Franz; Feger, Martina; Föller, Michael
Myostatin is a signaling molecule produced by skeletal muscle cells (myokine) that inhibits muscle hypertrophy and has further paracrine and endocrine effects in other organs including bone. Myostatin binds to activin receptor type 2B which forms a complex with transforming growth factor-β type I receptor (TGF-βRI) and induces intracellular p38MAPK and NFκB signaling. Fibroblast growth factor 23 (FGF23) is a paracrine and endocrine mediator produced by bone cells and regulates phosphate and vitamin D metabolism in the kidney. P38MAPK and NFκB-dependent store-operated Ca²⁺ entry (SOCE) are positive regulators of FGF23 production. Here, we explored whether myostatin influences the synthesis of FGF23. Fgf23 gene expression was determined by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast–like cells. UMR106 cells expressed activin receptor type 2A and B. Myostatin upregulated Fgf23 gene expression and protein production. The myostatin effect on Fgf23 was significantly attenuated by TGF-βRI inhibitor SB431542, p38MAPK inhibitor SB202190, and NFκB inhibitor withaferin A. Moreover, SOCE inhibitor 2-APB blunted the myostatin effect on Fgf23. Taken together, myostatin is a stimulator of Fgf23 expression in UMR106 cells, an effect at least partially mediated by downstream TGF-βRI/p38MAPK signaling as well as NFκB-dependent SOCE.
Nucleo-cytoplasmic shuttling of murine RBPJ by Hairless protein matches that of Su(H) protein in the model system Drosophila melanogaster
(2021) Wolf, Dorina B.; Maier, Dieter; Nagel, Anja C.
CSL transcription factors are central to signal transduction in the highly conserved Notch signaling pathway. CSL acts as a molecular switch: depending on the cofactors recruited, CSL induces either activation or repression of Notch target genes. Unexpectedly, CSL depends on its cofactors for nuclear entry, despite its role as gene regulator. In Drosophila, the CSL homologue Suppressor of Hairless (Su(H)), recruits Hairless (H) for repressor complex assembly, and eventually for nuclear import. We recently found that Su(H) is subjected to a dynamic nucleo-cytoplasmic shuttling, thereby strictly following H subcellular distribution. Hence, regulation of nuclear availability of Su(H) by H may represent a new layer of control of Notch signaling activity. Here we extended this work on the murine CSL homologue RBPJ. Using a ‘murinized’ fly model bearing RBPJwt in place of Su(H) at the endogenous locus we demonstrate that RBPJ protein likewise follows H subcellular distribution. For example, overexpression of a H*NLS3 protein variant defective of nuclear import resulted in a cytosolic localization of RBPJ protein, whereas the overexpression of a H*NES protein variant defective in the nuclear export signal caused the accumulation of RBPJ protein in the nucleus. Evidently, RBPJ is exported from the nucleus as well. Overall these data demonstrate that in our fly model, RBPJ is subjected to H-mediated nucleo-cytoplasmic shuttling as is Su(H). These data raise the possibility that nuclear availability of mammalian CSL proteins is likewise restricted by cofactors, and may hence present a more general mode of regulating Notch signaling activity.

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