Publications by authors named "Jana Schulz"

20 Publications

  • Page 1 of 1

FREQUENT LEPTOSPIRA SPP. DETECTION BUT ABSENCE OF TULA ORTHOHANTAVIRUS IN MICROTUS SPP. VOLES, NORTHWESTERN SPAIN.

J Wildl Dis 2021 Jul 28. Epub 2021 Jul 28.

Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

The common vole (Microtus arvalis) is a major agricultural pest in Europe and is a reservoir for several zoonotic agents, such as Leptospira spp. and Tula orthohantavirus (TULV). However, little is known about the occurrence of those pathogens in voles from Spain, where the species has largely expanded its distribution range in the past decades, causing agricultural pests and zoonotic diseases. For a molecular survey, 580 common voles and six Lusitanian pine voles (Microtus lusitanicus) were collected in 26 localities from four provinces of northwestern Spain. We assessed the presence of Leptospira spp. DNA in kidney tissue by PCR targeting the lipL32 gene, detecting a prevalence of 7.9% (95% confidence interval, 5.9-10.4) for common voles and of 33.3% (95% confidence interval, 4.3-77.7) for Lusitanian pine voles. We identified Leptospira kirschneri in 24 animals and Leptospira borgpetersenii in two animals, using secY gene-specific PCR. We analyzed environmental and demographic factors (such as age class, weight, and sex) and population dynamics data for their potential effect on the Leptospira spp. prevalence in those voles. The Leptospira spp. DNA detection rate in common voles increased significantly with maximum air temperature, vole weight, and amount of accumulated rainfall during the 90 d before capture and within the peak phase of the population cycle. We assessed the presence of TULV in lung tissue of 389 voles by reverse-transcription PCR, with no positive results. The absence of TULV might be explained by the evolutionary isolation of the common vole in Spain. The detection of two Leptospira genomospecies underlines the necessity for further typing efforts to understand the epidemiology of leptospiral infection in the common vole and the potential risk for human health in Spain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7589/JWD-D-20-00109DOI Listing
July 2021

A trans locus causes a ribosomopathy in hypertrophic hearts that affects mRNA translation in a protein length-dependent fashion.

Genome Biol 2021 06 28;22(1):191. Epub 2021 Jun 28.

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.

Background: Little is known about the impact of trans-acting genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate the influence of such distant genetic loci on the efficiency of mRNA translation and define their contribution to the development of complex disease phenotypes within a panel of rat recombinant inbred lines.

Results: We identify several tissue-specific master regulatory hotspots that each control the translation rates of multiple proteins. One of these loci is restricted to hypertrophic hearts, where it drives a translatome-wide and protein length-dependent change in translational efficiency, altering the stoichiometric translation rates of sarcomere proteins. Mechanistic dissection of this locus across multiple congenic lines points to a translation machinery defect, characterized by marked differences in polysome profiles and misregulation of the small nucleolar RNA SNORA48. Strikingly, from yeast to humans, we observe reproducible protein length-dependent shifts in translational efficiency as a conserved hallmark of translation machinery mutants, including those that cause ribosomopathies. Depending on the factor mutated, a pre-existing negative correlation between protein length and translation rates could either be enhanced or reduced, which we propose to result from mRNA-specific imbalances in canonical translation initiation and reinitiation rates.

Conclusions: We show that distant genetic control of mRNA translation is abundant in mammalian tissues, exemplified by a single genomic locus that triggers a translation-driven molecular mechanism. Our work illustrates the complexity through which genetic variation can drive phenotypic variability between individuals and thereby contribute to complex disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02397-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240307PMC
June 2021

Crimean-Congo hemorrhagic fever virus antibody prevalence in Mauritanian livestock (cattle, goats, sheep and camels) is stratified by the animal's age.

PLoS Negl Trop Dis 2021 04 12;15(4):e0009228. Epub 2021 Apr 12.

Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany.

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most widespread zoonotic arthropod-borne viruses in many parts of Africa, Europe and Asia. It belongs to the family of Nairoviridae in the genus of Orthonairovirus. The main reservoir and vector are ticks of the genus Hyalomma. Livestock animals (such as cattle, small ruminants and camels) develop a viremias lasting up to two weeks with absence of clinical symptoms, followed by seroconversion. This study was carried out to assess risk factors that affect seroprevalence rates in different species. In total, 928 livestock animal samples (cattle = 201; sheep = 247; goats = 233; camels = 247) from 11 out of 13 regions in Mauritania were assayed for CCHFV-specific immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assays (ELISA) (including a novel indirect camel-IgG-specific CCHFV ELISA). Inconclusive results were resolved by an immunofluorescence assay (IFA). A generalized linear mixed-effects model (GLMM) was used to draw conclusions about the impact of certain factors (age, species, sex and region) which might have influenced the CCHFV antibody status of surveyed animals. In goats and sheep, about 15% of the animals were seropositive, whereas in cattle (69%) and camels (81%), the prevalence rate was significantly higher. On average, cattle and camels were up to twice to four times older than small ruminants. Interestingly, the seroprevalence in all species was directly linked to the age of the animals, i.e. older animals had significantly higher seroprevalence rates than younger animals. The highest CCHFV seroprevalence in Mauritania was found in camels and cattle, followed by small ruminants. The large proportion of positive animals in cattle and camels might be explained by the high ages of the animals. Future CCHFV prevalence studies should at least consider the age of surveyed animals in order to avoid misinterpretations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0009228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081336PMC
April 2021

Serological and Molecular Investigation of Batai Virus Infections in Ruminants from the State of Saxony-Anhalt, Germany, 2018.

Viruses 2021 02 26;13(3). Epub 2021 Feb 26.

Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.

Arthropod-borne Batai virus (BATV) is an widely distributed throughout European livestock and has, in the past, been linked to febrile diseases in humans. In Germany, BATV was found in mosquitoes and in one captive harbor seal, and antibodies were recently detected in various ruminant species. We have, therefore, conducted a follow-up study in ruminants from Saxony-Anhalt, the most affected region in Eastern Germany. A total of 325 blood samples from apparently healthy sheep, goats, and cattle were tested using a BATV-specific qRT-PCR and SNT. Even though viral RNA was not detected, the presence of antibodies was confirmed in the sera of all three species: sheep (16.5%), goats (18.3%), and cattle (41.4%). Sera were further analyzed by a glycoprotein Gc-based indirect ELISA to evaluate Gc-derived antibodies as a basis for a new serological test for BATV infections. Interestingly, the presence of neutralizing antibodies was not directly linked to the presence of BATV Gc antibodies. Overall, our results illustrate the high frequency of BATV infections in ruminants in Eastern Germany.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13030370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996813PMC
February 2021

A Synthetic Modified Live Chimeric Marker Vaccine against BVDV-1 and BVDV-2.

Vaccines (Basel) 2020 Oct 2;8(4). Epub 2020 Oct 2.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.

Bovine viral diarrhea virus (BVDV), a pestivirus which exists in the two distinct species BVDV-1 (syn. ) and BVDV-2 (syn. ), is the causative agent of one of the most widespread and economically important virus infections in cattle. For economic as well as for animal health reasons, an increasing number of national BVDV control programs were recently implemented. The main focus lies on the detection and removal of persistently infected cattle. The application of efficient marker or DIVA (differentiation of infected from vaccinated animals) vaccines would be beneficial for the eradication success in regions with a high BVDV prevalence to prevent fetal infection and it would allow serological monitoring of the BVDV status also in vaccinated farms. Therefore, a marker vaccine based on the cytopathic (cp) BVDV-1b strain CP7 was constructed as a synthetic backbone (BVDV-1b_synCP7). For serological discrimination of vaccinated from infected animals, the viral protein E was substituted by the heterologous E of Bungowannah virus (BuPV, species ). In addition, the vaccines were attenuated by a deletion within the type I interferon inhibitor N protein encoding sequence. The BVDV-2 vaccine candidate is based on the genetic sequence of the glycoproteins E1 and E2 of BVDV-2 strain CS8644 (CS), which were introduced into the backbone of BVDV-1b_synCP7_ΔN_E Bungo in substitution of the homologous glycoproteins. Vaccine virus recovery resulted in infectious cytopathic virus chimera that grew to titers of up to 10 TCID/mL. Both synthetic chimera BVDV-1b_synCP7_ΔN_E Bungo and BVDV-1b_synCP7_ΔN_E Bungo_E1E2 BVDV-2 CS were avirulent in cattle, provided a high level of protection in immunization and challenge experiments against both BVDV species and allowed differentiation of infected from vaccinated cattle. Our study presents the first report on an efficient BVDV-1 and -2 modified live marker vaccine candidate and the accompanying commercially available serological marker ELISA system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines8040577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712951PMC
October 2020

Hunters' Acceptance of Measures against African Swine Fever in Wild Boar in Estonia.

Prev Vet Med 2020 Sep 11;182:105121. Epub 2020 Aug 11.

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, Südufer 10, 17493, Greifswald-Insel Riems, Germany. Electronic address:

African swine fever (ASF) was first identified in Estonia in 2014, initially detected in wild boar and spreading to affect almost the whole country from late 2016 onwards. Passive surveillance and the control measures applied in Estonia are the main actions in the attempt to control the wild boar population and therefore limit the spread of ASF. Implementation and success of both activities depend mainly on the involvement and commitment of the executing force: the Estonian hunters. Thus, their acceptance of the measures is of utmost importance and with the help of participatory methods, their acceptability can be assessed. Participatory epidemiology allows the involvement of key stakeholders in planning control measures and surveillance strategies and gathering information otherwise inaccessible. By conducting focus group discussions and utilizing participatory tools, this study aimed to assess the acceptance of ASF control measures by hunters in Estonia. Furthermore, the study aimed to detect means to improve the motivation of hunters to support passive surveillance. Among hunters, the results ranked the trust in lower authorities (e.g. local official veterinarians) towards implementing control measures as high (in contrast to higher officials e.g. 'Ministry of Rural Affairs'), while perceiving themselves as the most trustworthy group among those implementing ASF control measures. Hunting and every measure supporting increased hunting, for example selective hunting, bait feeding and incentives for hunting wild boar, were deemed favourable for hunters. These measures also received the highest trust for controlling ASF. All measures hindering hunting and the movement of wildlife, for example fencing or involvement of the army in ASF control, were described as unpleasant or even unethical and trust in these measures to control the disease successfully was lacking. When assessing the perceived consequences for hunters of finding a dead wild boar, arising financial costs, additional workload and time consumption were highlighted. In line with these results, the two tools with the strongest motivational effect for taking part in passive surveillance were: (1) higher monetary incentives as compensation for the hunters' work, and (2) the reduction of the negative consequences by limiting the hunters' duties to solely reporting found dead wild boar. In conclusion, participatory methods can be used as a highly suitable tool for the evaluation of acceptance of measures and surveillance systems. Potentially, the results can help to improve control and passive surveillance in Estonia, as well as functioning as an example for other countries battling or awaiting ASF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prevetmed.2020.105121DOI Listing
September 2020

A human ESC-based screen identifies a role for the translated lncRNA in pancreatic endocrine differentiation.

Elife 2020 08 3;9. Epub 2020 Aug 3.

Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, San Diego, United States.

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion of diminishes insulin cells, in a manner independent of the nearby TF . One-by-one disruption of each of 's open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic differentiation and provides a blueprint for dissection of their coding and noncoding roles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.58659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423336PMC
August 2020

West Nile Virus Lineage 2 Vector Competence of Indigenous and Mosquitoes from Germany at Temperate Climate Conditions.

Viruses 2020 05 19;12(5). Epub 2020 May 19.

Institute of Infectology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.

West Nile virus (WNV) is a widespread zoonotic arbovirus and a threat to public health in Germany since its first emergence in 2018. It has become of particular relevance in Germany in 2019 due to its rapid geographical spread and the detection of the first human clinical cases. The susceptibility of indigenous (biotypes and ) for a German WNV lineage 2 strain was experimentally compared to that of Serbian biotype and invasive German . All tested populations proved to be competent laboratory vectors of WNV. biotype displayed the highest transmission efficiencies (40.0%-52.9%) at 25 °C. This biotype was also able to transmit WNV at 18 °C (transmission efficiencies of 4.4%-8.3%), proving that temperate climates in Central and Northern Europe may support WNV circulation. Furthermore, due to their feeding behaviors, biotype and can act as "bridge vectors", leading to human WNV infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12050561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291008PMC
May 2020

Risk-based eradication as a control measure to limit the spread of LA-MRSA among Danish pig herds - a simulation study.

Sci Rep 2019 09 13;9(1):13192. Epub 2019 Sep 13.

University of Copenhagen, Faculty of Health Sciences, Grønnegårdsvej 8, 1870, Frederiksberg C, Denmark.

A national screening in 2016 identified 88% of Danish pig herds positive for livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). This highlights the importance of evaluating potential control measures that could reduce the prevalence of LA-MRSA among Danish pig herds. In addition to describing the effects of (1) reduced within-herd transmission, (2) increased biosecurity, and (3) movement restrictions, the eradication of LA-MRSA as a potential control measure was investigated using a simulation model mimicking the spread of LA-MRSA among pig herds between 2006 and 2015. The latter strategy was simulated either as eradication of a random selection of herds for surveillance or as a risk-based selection of herds based on their potential to spread LA-MRSA via pig movements in four different scenarios: low- vs. high-prevalence scenarios with control measures starting in 2007 and in 2010. Almost all control measures showed the potential to reduce the spread of LA-MRSA among pig herds, especially when implemented intensively and when control measures were combined. Risk-based selection of herds for eradication led to a greater relative reduction compared to random selection. In the high-prevalence scenario in particular, combinations including risk-based eradication led to the greatest relative reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-49752-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744507PMC
September 2019

The Translational Landscape of the Human Heart.

Cell 2019 06 30;178(1):242-260.e29. Epub 2019 May 30.

Department of Rheumatology and Clinical Immunology, Sapporo City General Hospital, Sapporo, Hokkaido 060-8604, Japan.

Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, suggesting inefficient translation termination. We identify hundreds of previously undetected microproteins, expressed from lncRNAs and circRNAs, for which we validate the protein products in vivo. The translation of microproteins is not restricted to the heart and prominent in the translatomes of human kidney and liver. We associate these microproteins with diverse cellular processes and compartments and find that many locate to the mitochondria. Importantly, dozens of microproteins are translated from lncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2019.05.010DOI Listing
June 2019

Meso scale discovery-based assays for the detection of aggregated huntingtin.

PLoS One 2019 26;14(3):e0213521. Epub 2019 Mar 26.

CHDI Management/CHDI Foundation, Los Angeles, CA, United States of America.

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin (HTT) gene, leading to an expanded poly-glutamine (polyQ) stretch in the HTT protein. This mutant HTT (mHTT) protein is highly prone to intracellular aggregation, causing significant damage and cellular loss in the striatal, cortical, and other regions of the brain. Therefore, modulation of mHTT levels in these brain regions in order to reduce intracellular mHTT and aggregate levels represents a direct approach in the development of HD therapeutics. To this end, assays that can be used to detect changes in HTT levels in biological samples are invaluable tools to assess target engagement and guide dose selection in clinical trials. The Meso Scale Discovery (MSD) ELISA-based assay platform is a robust and sensitive method previously employed for the quantification of HTT. However, the currently available MSD assays for HTT are primarily detecting the monomeric soluble form of the protein, but not aggregated species. In this study, we describe the development of novel MSD assays preferentially detecting mHTT in an aggregated form. Recombinant monomeric HTT(1-97)-Q46, which forms aggregates in a time-dependent manner, was used to characterize the ability of each established assay to distinguish between HTT monomers and HTT in a higher assembly state. Further validation of these assays was performed using brain lysates from R6/2, zQ175 knock-in, and BACHD mouse models, to replicate a previously well-characterized age-dependent increase in brain aggregate signals, as well as a significant reduction of aggregate levels in the striatum following mHTT knockdown with a CAG-directed allele-specific zinc-finger repressor protein (ZFP). Lastly, size exclusion chromatography was used to separate and characterize HTT species from brain tissue lysates to demonstrate specificity of the assays for the fractions containing aggregated HTT. In summary, we demonstrate that the newly developed assays preferentially detect aggregated HTT with improved performance in comparison to previous assay technologies. These assays complement the existing MSD platform assays specific for soluble HTT monomers, allowing for a more comprehensive analysis of disease-relevant HTT species in preclinical models of HD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213521PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435127PMC
December 2019

Effects of control measures on the spread of LA-MRSA among Danish pig herds between 2006 and 2015 - a simulation study.

Sci Rep 2019 01 24;9(1):691. Epub 2019 Jan 24.

Technical University of Denmark, National Veterinary Institute, Kemitorvet, Building 204, 2800 Kgs., Lyngby, Denmark.

There has been a rapid increase in Danish pig herds testing positive for livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA) since the first screening in 2008. Despite a national action plan to control LA-MRSA in the Danish pig population, 88% of pig herds tested positive in a 2016 cross-sectional study of 57 herds. The national action plan was initiated in April 2015 and aimed to reduce the spread of LA-MRSA among pig herds. However, its success is uncertain. We used a simulation model mimicking the spread of LA-MRSA among pig herds between 2006 and 2015 to evaluate the impact of control strategies if these had these been implemented in 2007 or 2010. The strategies were combinations of the following control measures: (1) a reduced number of herds using high-risk antibiotics, (2) a reduced probability of indirect transmission among herds via humans, (3) movement restrictions, and (4) voluntary eradication in 5-7.5% of the herds. Almost all tested control strategies simulated a reduction in the spread of LA-MRSA. The combination of two, three or four intervention strategies showed additive effects and led to larger reductions in the predicted herd prevalence. In addition, the prevalence of LA-MRSA-positive herds at the time when control measures were initiated influenced the effects of the control strategies. Combining the simulated control measures can be considered in future action plans to control LA-MRSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-37075-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346033PMC
January 2019

Detection of Francisella tularensis in three vole species in Central Europe.

Transbound Emerg Dis 2019 Mar 8;66(2):1029-1032. Epub 2019 Jan 8.

Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany.

Francisella tularensis is a zoonotic, gram-negative bacterium that causes tularemia in humans. Depending on its subspecies and the route of transmission, mild to lethal courses have been reported. F. tularensis subsp. holarctica is the only subspecies found in Europe and affects a plenitude of vertebrates including lagomorphs and rodents. Population outbreaks of certain rodent species are likely to be involved in the transmission of this pathogen. This molecular survey aims to evaluate the presence of F. tularensis in small mammals from three Central European countries. Using a real-time polymerase chain reaction, F. tularensis DNA was detected in common voles (Microtus arvalis) from Switzerland and in field voles (Microtus agrestis) and a bank vole (Myodes glareolus) from Germany, but not in any other small mammal species. All common voles from the Czech Republic were negative for F. tularensis DNA. The prevalence in the three vole species varied between 1.3% and 3.0%. In conclusion, Francisella tularensis DNA was detected in three vole species in two of three countries investigated. The observed low prevalence raises questions on the role of voles for the transmission of Francisella tularensis in Central Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbed.13078DOI Listing
March 2019

Drivers for Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Spread Among Danish Pig Herds - A Simulation Study.

Sci Rep 2018 11 16;8(1):16962. Epub 2018 Nov 16.

National Veterinary Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

To gain insight into the rapid increase in the number of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA)-positive herds in Denmark, we developed an individual-based Monte Carlo simulation model. We aimed to assess whether transmission of LA-MRSA via pig movements could explain the observed increase in the number of positive herds in Denmark, and to evaluate the effect of other between-herd transmission mechanisms. Pig movements alone were not sufficient to mimic the observed increase in LA-MRSA-positive herds in Denmark in any of the modelled scenarios. The model identified three factors that played important roles in the between-herd spread of LA-MRSA: (1) the within-herd dynamics, (2) the frequency and effectiveness of indirect transmissions, and (3) unexplainable introduction of LA-MRSA to swine herds. These factors can act as starting points for the development of LA-MRSA control programs in pig herds in order to limit the risk of its transmission to humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-34951-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240036PMC
November 2018

Drivers and Dynamics of Methicillin-Resistant Livestock-Associated Staphylococcus aureus CC398 in Pigs and Humans in Denmark.

mBio 2018 11 13;9(6). Epub 2018 Nov 13.

Statens Serum Institut, Copenhagen, Denmark

The spread of livestock-associated methicillin-resistant clonal complex 398 (LA-MRSA CC398) within the Danish pig production system has been linked to an increased number of human infections. Yet, the population structure and transmission dynamics of this important pathogen remain poorly understood. In this study, whole-genome sequences from 371 LA-MRSA CC398 isolates collected between 2004 and 2015 were subjected to bioinformatic analyses. The isolates originated from Danish pig farms ( = 209) and people having livestock contact ( = 79). In addition, whole-genome sequence data from 82 isolates representing an international reference collection and 83 isolates from Danish patients were included in the analysis. The results demonstrated that the increasing prevalence of LA-MRSA CC398 in Danish pigs and patients was caused by clonal expansion of three dominant lineages. The results also showed that these lineages were enriched for the tetracycline resistance gene (K) and other determinants conferring resistance to some of the most frequently used antimicrobials in Danish pigs. The association between pig movements and the spread of LA-MRSA CC398 was assessed in a Poisson regression analysis of 17,009 pig movements into 273 farms with known LA-MRSA CC398 status. The results demonstrated that animal movements have played a critical role in the dissemination of LA-MRSA CC398 within the Danish pig production system, although other transmission routes may also have contributed. Consistent with this scenario, the genetic relatedness of isolates from different farms was positively correlated with the number of animal movements between the farms. Livestock-associated methicillin-resistant clonal complex CC398 (LA-MRSA CC398) is resistant to nearly all β-lactams and several non-β-lactam antimicrobials. Over the last decade, it has become widespread in pig farms across Europe and is now an important cause of human infections in countries with previously low levels of MRSA, such as the Netherlands and Denmark. The hitherto uncontrolled spread of LA-MRSA CC398 underscores an urgent need to understand its epidemiology in order to develop evidence-based interventions. This study demonstrates that pig movements between farms in combination with increased bacterial resistance to specific antibiotics and heavy metals were important drivers of the rapid spread of LA-MRSA CC398 in the Danish pig production system. These findings should be taken into consideration when researchers and policy makers evaluate and decide on actions and policies to limit the spread of LA-MRSA CC398 and other pathogens in food animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.02142-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234867PMC
November 2018

Methods to Study the Roles of Rho GTPases in Dendritic Tree Complexity.

Methods Mol Biol 2018 ;1821:297-317

Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany.

Most neurons elaborate a characteristic dendritic arbor which is physiologically important for receiving and processing of synaptic inputs. Pathologically, disturbances in the regulation of dendritic tree complexity are often associated with mental retardation and other neurological deficits. Rho GTPases are major players in the regulation of dendritic tree complexity. They are involved in many signal transduction cascades, activated at the neuronal plasma membrane, and relayed to intracellular proteins that directly rearrange the cytoskeleton. The use of siRNA technology combined with morphometric and imaging techniques allows the roles of individual Rho GTPases, such as Rac1, in dendritic branching to be examined. In this chapter we describe the establishment, transfection, and processing of a primary hippocampal cell culture. Methods to assess the complexity of dendritic arbors like the Sholl analysis, and techniques to investigate Rac1 activity in hippocampal cells, and specifically in neuronal dendrites, such as fluorescence resonance energy transfer (FRET) imaging are presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-8612-5_21DOI Listing
March 2019

Network analysis of pig movements: Loyalty patterns and contact chains of different holding types in Denmark.

PLoS One 2017 29;12(6):e0179915. Epub 2017 Jun 29.

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, Greifswald, Insel Riems, Germany.

Understanding animal movements is an important factor for the development of meaningful surveillance and control programs, but also for the development of disease spread models. We analysed the Danish pig movement network using static and temporal network analysis tools to provide deeper insight in the connection between holdings dealing with pigs, such as breeding and multiplier herds, production herds, slaughterhouses or traders. Pig movements, which occurred between 1st January 2006 and 31st December 2015 in Denmark, were summarized to investigate temporal trends such as the number of active holdings, the number of registered movements and the number of pigs moved. To identify holdings and holding types with potentially higher risk for introduction or spread of diseases via pig movements, we determined loyalty patterns, annual network components and contact chains for the 24 registered holding types. The total number of active holdings as well as the number of pig movements decreased during the study period while the holding sizes increased. Around 60-90% of connections between two pig holdings were present in two consecutive years and around one third of the connections persisted within the considered time period. Weaner herds showed the highest level of in-loyalty, whereas we observed an intermediate level of in-loyalty for all breeding sites and for production herds. Boar stations, production herds and trade herds showed a high level of out-loyalty. Production herds constituted the highest proportion of holdings in the largest strongly connected component. All production sites showed low levels of in-going contact chains and we observed a high level of out-going contact chain for breeding and multiplier herds. Except for livestock auctions, all transit sites also showed low levels of out-going contact chains. Our results reflect the pyramidal structure of the underlying network. Based on the considered disease, the time frame for the calculation of network measurements needs to be adapted. Using these adapted values for loyalty and contact chains might help to identify holdings with high potential of spreading diseases and thus limit the outbreak size or support control or eradication of the considered pathogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179915PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491064PMC
September 2017

Surveillance strategies for Classical Swine Fever in wild boar - a comprehensive evaluation study to ensure powerful surveillance.

Sci Rep 2017 03 7;7:43871. Epub 2017 Mar 7.

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

Surveillance of Classical Swine Fever (CSF) should not only focus on livestock, but must also include wild boar. To prevent disease transmission into commercial pig herds, it is therefore vital to have knowledge about the disease status in wild boar. In the present study, we performed a comprehensive evaluation of alternative surveillance strategies for Classical Swine Fever (CSF) in wild boar and compared them with the currently implemented conventional approach. The evaluation protocol was designed using the EVA tool, a decision support tool to help in the development of an economic and epidemiological evaluation protocol for surveillance. To evaluate the effectiveness of the surveillance strategies, we investigated their sensitivity and timeliness. Acceptability was analysed and finally, the cost-effectiveness of the surveillance strategies was determined. We developed 69 surveillance strategies for comparative evaluation between the existing approach and the novel proposed strategies. Sampling only within sub-adults resulted in a better acceptability and timeliness than the currently implemented strategy. Strategies that were completely based on passive surveillance performance did not achieve the desired detection probability of 95%. In conclusion, the results of the study suggest that risk-based approaches can be an option to design more effective CSF surveillance strategies in wild boar.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep43871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339697PMC
March 2017

Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

J Neurochem 2016 10 4;139(1):26-39. Epub 2016 Aug 4.

Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany.

Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form of the GTPase Cdc42 decreases dendritic branching. CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic branching. Thus, CALEB/NGC organizes a Rho GTPase signaling module at the plasma membrane for shaping dendritic trees.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jnc.13735DOI Listing
October 2016

Structural Basis for the Functional Coupling of the Alternative Splicing Factors Smu1 and RED.

Structure 2016 05 14;24(5):762-773. Epub 2016 Apr 14.

Laboratory of Structural Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany. Electronic address:

The proteins Smu1 and RED have been jointly implicated in the regulation of alternative splicing, mitosis, and influenza virus infection, but how they interact and whether their diverse cellular functions are coupled is unknown. We identified an N-terminal region of Smu1 and a central region of RED that stably interact. Structural analyses revealed that the RED-binding region of Smu1 contains an N-terminal LisH motif linked to a core domain and a C-terminal α helix that folds back onto the LisH motif. Smu1 dimerizes via its LisH motif and C-terminal α helix and undergoes global conformational changes upon RED binding. In the ensuing hetero-tetrameric Smu1-RED complex, two molecules of RED use short α helices to bind hydrophobic grooves of two Smu1 core domains. Our results show how Smu1 and RED form a functional module that exhibits intriguing similarities to transcriptional co-repressor complexes, arranging multiple additional protein-protein interaction sites for contacting splicing and/or chromatin factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.str.2016.03.016DOI Listing
May 2016
-->