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Haemotrophic mycoplasmas (haemoplasmas) are a group of highly specific and adapted bacteria. Three different haemoplasma species in pigs are known to date: Mycoplasma (M.) suis, M. parvum and ‘Candidatus (Ca.) M. haemosuis’. Even though these bacteria have been known in pig farming for a long time, it is difficult to draw general conclusions about the relevance of their infections in pigs. This review summarizes the current knowledge on the three porcine haemoplasma species with regards to clinical and pathological descriptions, pathobiology, epidemiology and diagnostics as well as prevention and therapy. Overall, it is clear that considerably more data are available for M. suis than for the other two species, but generally, porcine haemoplasmas were found to be highly prevalent all over the world. Mycoplasma suis is the most virulent species, causing acute infectious anaemia in pigs (IAP), whereas M. parvum usually results in chronic and subclinical infections associated with performance losses. Little is known about the clinical significance of the recently discovered third porcine species ‘Ca. M. haemosuis’. So far, the described pathogenic mechanisms mainly include direct destruction of erythrocytes via adhesion, invasion, eryptosis and nutrient scavenging, indirect erythrocyte lysis due to immune-mediated events and immune dysregulation processes. A review of published diagnostic data confirms PCR assays as the current standard method, with various cross-species and species-specific protocols. Overall, there is a need for further examination to obtain valuable insights for practical application, specifically regarding the importance of subclinical infections in naturally infected animals. An essential requirement for this will be to gain a more comprehensive understanding of the mechanisms operating between the host and the pathogen.

Hemotrophic mycoplasmas (HMs) are highly host-adapted and specialized pathogens infecting a wide range of mammals including farm animals, i.e., pigs, cattle, sheep, and goats. Although HMs have been known for over 90 years, we still do not know much about the natural transmission routes within herds. Recently, it has been repeatedly discussed in publications that arthropod vectors may play a role in the transmission of HMs from animal to animal. This is mainly since several HM species could be detected in different potential arthropod vectors by PCR. This review summarizes the available literature about the transmission of bovine, porcine, ovine, and caprine HM species by different hematophagous arthropod vectors. Since most studies are only based on the detection of HMs in potential vectors, there are rare data about the actual vector competence of arthropods. Furthermore, there is a need for additional studies to investigate, whether there are biological vectors in which HMs can multiply and be delivered to new hosts.

Abstract Background The appearance of the novel porcine haemotrophic mycoplasma (HM) species ‘Candidatus Mycoplasma haemosuis’ was reported in apparently healthy but also in clinically sick animals in China, Korea and in a case report from Germany. Outside of Asia, however, nothing further is known about the frequency of ‘Ca. M. haemosuis’ in pigs to date. To investigate the distribution of this novel HM species in Germany, fattening pigs, sows and pre-suckling piglets were examined using a herein developed quantitative real-time PCR assay (qPCR). Because the piglets were sampled before the first colostrum uptake, additional information on a possible vertical transmission from dams to their offspring was obtained. Results Our novel qPCR assay successfully detected ‘Ca. M. haemosuis’ in all blood samples from the ‘Ca. M. haemosuis’-infected pigs. No cross-reactivity was detected when DNA from non-target Mycoplasma spp. and other bacterial species representing 105 bacteria/reaction were used as a template. The lower limit of detection of the qPCR was thus 10 gap gene copies per reaction and 2.5 x 103 genome equivalents (GE) per mL blood. ‘Candidatus M. haemosuis’ was detected by this qPCR in blood samples from a total out of 6.25% sows (13/208), 4.50% pre-suckling piglets (28/622) and 17.50% fattening pigs (35/200). On farm level, 3 out of 21 piglet producing farms (14.28%) and 9 out of 20 fattening farms (45.00%) were positive for ‘Ca. M. haemosuis’. Co-infections with M. suis were evident in all age groups. Conclusion ‘Candidatus M. haemosuis’ infection is present in German pig farms and the detection of the novel porcine HM species in piglets immediately after birth before colostrum intake indicates vertical transmission. The novel qPCR assay specific for ‘Ca. M. haemosuis’ described herein will be a prerequisite for future studies on the prevalence, epidemiology as well as the clinical and economic impact of ‘Ca. M. haemosuis’ infections.

Antimicrobial resistance is one of the most crucial One Health topics worldwide. Consequently, various national and international surveillance programs collect data and report trends regularly. Ceftiofur, colistin and enrofloxacin belong to the most important and critical class of anti-infective medications in both human and veterinary medicine. In the present study, antimicrobial resistance was analyzed using the epidemiological cut-off (ECOFF) value on 6569 Escherichia coli isolated from pigs in Bavaria, Germany, during five years, from 2016 to 2020. The statistically relevant results regarding antimicrobial resistance revealed a decrease for colistin, an increase for enrofloxacin, and a constant level for ceftiofur. In Germany, the usage of all three antimicrobial substances in livestock has fallen by 43.6% for polypeptides, 59.0% for fluoroquinolones and 57.8% for the 3rd + 4th generation cephalosporines during this time. Despite the decline in antimicrobial usage, a reduction regarding antimicrobial resistance was solely observed for colistin. This finding illustrates that in addition to the restriction of pharmaceutical consumption, further measures should be considered. Improved biosecurity concepts, a reduction in crowding, and controlled animal movements on farms may play a key role in finally containing the resistance mechanisms of bacteria in farm animals.

Abstract Horizontal transmission of Mycoplasma suis via parenteral exposure during standard practices or through bites during fightings have been identified as key epidemiological routes. However, as knowledge gaps on other potential shedding and transmission routes exist, the present study combines both laboratory experiments and field surveys to gain new insights into the epidemiology of porcine haemotrophic mycoplasmas. Splenectomised pigs were orally inoculated with a M. suis field strain and investigated for clinical signs related to infectious anaemia of pigs (IAP) and the presence of M. suis in blood, urine and saliva samples by qPCR. All blood samples were negative for M. suis and animals did not show obvious clinical signs of IAP throughout the entire study period. Additionally, urine, nasal and saliva samples from sows of conventional piglet producing farms and semen samples from a boar stud revealed no detection of M. suis and ‘Candidatus Mycoplasma haemosuis’ by qPCR. Thus, the results indicate that blood-independent transmission routes might be of minor relevance under field conditions.

Abstract Background Mycoplasma suis (M. suis) belongs to the group of haemotrophic mycoplasmas and is known as the causative agent of infectious anaemia in pigs. In the last few years valuable insights into the mechanism of adhesion and invasion, shedding patterns and cell tropism of M. suis were gained by the use of new molecular techniques. However, details on M. suis induced lesions as well as the distribution of M. suis in different organs are still lacking. Therefore, seven splenectomised pigs were experimentally infected and clinical and laboratory investigations as well as a detailed histopathological examination were performed. Detection and quantification of M. suis DNA in blood and various tissue samples was done using a quantitative real-time PCR. Results During the course of experimental infection, periodically occurring signs of infectious anaemia of pigs including severe icteroanaemia, fever, apathy and anorexia were observed. In addition, dermatological manifestations such as haemorrhagic diathesis presenting as petechiae occurred. The most important haematological alterations were normochromic, normocytic anaemia, hypoglycaemia as well as increased bilirubin and urea concentrations. Necropsy revealed predominant evidence of haemolysis with consecutive anaemia, as well as disseminated intravascular coagulation. M. suis was found in all investigated tissues with the highest copy numbers found in the kidneys. In Giemsa stained sections M. suis was only detected red blood cell (RBC)-associated. Conclusion In the present study, no RBC independent sequestration of M. suis was detected in organs of experimentally infected pigs. Pathological findings are most likely resulting from haemolysis, consecutive anaemia as well as from disseminated intravascular coagulation and subsequent organ impairments.

Mycoplasma (M.) parvum is a hemotrophic bacterium circulating in the blood of pigs but is not considered a primary pathogen. Only a handful of studies dealing with this agent have been published since its first description in 1951, and many issues, including epidemiology and the impact of subclinical infections, are yet to be elucidated. This study aimed to establish a M. parvum specific real-time PCR for its detection and quantification in porcine blood and the application of this assay to obtain insights into the occurrence of M. parvum in German pigs. Furthermore, 16S rDNA amplicons of M. parvum positive blood samples were phylogenetically analyzed using MEGA 11 software. The established qPCR targeting the M. parvum glyceraldehyde-3-phosphate dehydrogenase encoding gene (gap) showed a lower detection limit of 10 gene copies per reaction and no cross-reactivity within the specificity test. A total of 36.0% (n = 72) of the sampled fattening pigs, 25.0% (n = 15) of the sows, and 4.37% (n = 8) of the boars tested M. parvum positive. The dendrogram showed the typical allocation of the M. parvum isolates into the “haemominutum group” subgroup within the hemotrophic Mycoplasma species. Both the novel established qPCR and the obtained epidemiological data can serve as an important basis for future studies dealing with M. parvum.

Abstract Background Transmission of Mycoplasma (M.) suis mainly occurs via iatrogenic or zootechnical manipulations or due to ranking fights. Other transmission routes including ingestion of secretes/excretes; blood-sucking arthropods and intra-uterine transmission have thought to play an epidemiological role without being experimentally proven. To investigate a vertical transmission of M. suis under field conditions blood samples from pre-suckling piglets and their corresponding dam were examined for M. suis by quantitative polymerase chain reaction (qPCR) in 21 farms in Southern Germany. Results A total of 14.35% of the 474 blood samples from pre-suckling piglets reacted qPCR positive. Additionally, M. suis was detected in 65 (31.25%) of the 208 sows at farrowing. On farm level, 16 (76.2%) of the 21 farms had at least one M. suis positive animal. M. suis positive farms had an average of 0.41 more stillborn piglets per litter than M. suis negative farms (p = 0.007). Conclusion The present study provides further insights into M. suis infection dynamics as it is the first detection of M. suis in piglets immediately after birth prior to colostrum intake and the first large scale investigation of M. suis in sows at farrowing.

Abstract Background The significance of hemotrophic mycoplasma in cattle remains unclear. Especially in Europe, their epidemiological parameters as well as pathophysiological influence on cows are lacking. The objectives of this study were: (1) to describe the prevalence of ‘Candidatus Mycoplasma haemobos’ (‘C. M. haemobos’) and Mycoplasma wenyonii (M. wenyonii) in Bavaria, Germany; (2) to evaluate their association with several blood parameters; (3) to explore the potential of vertical transmission in Simmental cattle; and (4) to evaluate the accuracy of acridine-orange-stained blood smears compared to real-time polymerase chain reaction (PCR) results to detect hemotrophic mycoplasma. A total of 410 ethylenediaminetetraacetic acid-blood samples from cows from 41 herds were evaluated by hematology, acridine-orange-stained blood smears, and real-time PCR. Additionally, blood samples were taken from dry cows of six dairy farms with positive test results for hemotrophic mycoplasma to investigate vertical transmission of infection. Results The period prevalence of both species was 60.24% (247/410), C. M. haemobos 56.59% (232/410), M. wenyonii 8.54% (35/410) and for coinfection 4.88% (20/410). Of the relevant blood parameters, only mean cell volume (MCV), mean cell hemoglobin (MCH), and white blood cell count (WBC) showed differences between the groups of infected and non-infected individuals. There were lower values of MCV (P

Lifespan analyses are important for advancing our understanding of the aging process. There are two major issues in performing lifespan studies: 1) late-stage animal lifespan analysis may include animals with non-terminal, yet advanced illnesses, which can pronounce indirect processes of aging rather than the aging process per se and 2) they often involves challenging welfare considerations. Herein, we present an option to the traditional way of performing lifespan studies by using a novel method that generates high-quality data and allows for the inclusion of excluded animals, even animals removed at early signs of disease. This Survival-span method is designed to be feasibly done with simple means by any researcher and strives to improve the quality of aging studies and increase animal welfare.

Abstract The term Anthropocene initially emerged from the Earth System science community in the early 2000s, denoting a concept that the Holocene Epoch has terminated as a consequence of human activities. First associated with the onset of the Industrial Revolution, it was then more closely linked with the Great Acceleration in industrialization and globalization from the 1950s that fundamentally modified physical, chemical, and biological signals in geological archives. Since 2009, the Anthropocene has been evaluated by the Anthropocene Working Group, tasked with examining it for potential inclusion in the Geological Time Scale. Such inclusion requires a precisely defined chronostratigraphic and geochronological unit with a globally synchronous base and inception, with the mid‐twentieth century being geologically optimal. This reflects an Earth System state in which human activities have become predominant drivers of modifications to the stratigraphic record, making it clearly distinct from the Holocene. However, more recently, the term Anthropocene has also become used for different conceptual interpretations in diverse scholarly fields, including the environmental and social sciences and humanities. These are often flexibly interpreted, commonly without reference to the geological record, and diachronous in time; they often extend much further back in time than the mid‐twentieth century. These broader conceptualizations encompass wide ranges and levels of human impacts and interactions with the environment. Here, we clarify what the Anthropocene is in geological terms and compare the proposed geological (chronostratigraphic) definition with some of these broader interpretations and applications of the term “Anthropocene,” showing both their overlaps and differences.

Abstract Background The proteasome system plays an important role in synaptic plasticity. Induction and maintenance of long term potentiation is directly dependent on selective targeting of proteins for proteasomal degradation. The 20S proteasome activator PA28αβ activates hydrolysis of small nonubiquitinated peptides and possesses protective functions upon oxidative stress and proteinopathy. The effect of PA28αβ activity on behavior and memory function is, however, not known. We generated a mouse model that overexpresses PA28α (PA28αOE) to understand PA28αβ function during healthy adult homeostasis via assessment of physiological and behavioral profiles, focusing on female mice. Results PA28α and PA28β protein levels were markedly increased in all PA28αOE tissues analyzed. PA28αOE displayed reduced depressive-like behavior in the forced swim test and improved memory/learning function assessed by intersession habituation in activity box and shuttle box passive avoidance test, with no significant differences in anxiety or general locomotor activity. Nor were there any differences found when compared to WT for body composition or immuno-profile. The cognitive effects of PA28αOE were female specific, but could not be explained by alterations in estrogen serum levels or hippocampal regulation of estrogen receptor β. Further, there were no differences in hippocampal protein expression of neuronal or synaptic markers between PA28αOE and WT. Biochemical analysis of hippocampal extracts demonstrated that PA28α overexpression did not increase PA28–20S peptidase activity or decrease K48-polyubiquitin levels. Instead, PA28αOE exhibited elevated efficiency in preventing aggregation in the hippocampus. Conclusions This study reveals, for the first time, a connection between PA28αβ and neuronal function. We found that PA28α overexpressing female mice displayed reduced depressive-like behavior and enhanced learning and memory. Since the positive effects of PA28α overexpression arose without an activation of 20S proteasome capacity, they are likely independent of PA28αβ’s role as a 20S proteasome activator and instead depend on a recognized chaperone-like function. These findings suggest that proteostasis in synaptic plasticity is more diverse than previously reported, and demonstrates a novel function of PA28αβ in the brain.

OBJECTIVES: Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation which is associated with a series of methodological caveats. Knowledge of circadian cortisol patterns and cortisol awakening response (CAR) is still limited. METHODS: A total of 77 MS patients (55 relapsing-remitting MS (RRMS)/22 secondary-progressive MS (SPMS)) as well as 34 healthy control (HC) subjects were enrolled. Diurnal cortisol release was assessed by repeated salivary cortisol sampling. Neurological disability was rated by the Kurtzke's Expanded Disability Status Scale (EDSS). Depressive symptoms and perceived stress were assessed by self-report measures. RESULTS: RRMS but not SPMS patients differed in circadian cortisol release from HC subjects. Differences in cortisol release were restricted to CAR. Treated and treatment naïve RRMS patients did not differ in CAR. In a RRMS follow-up cohort (nine months follow-up), RRMS patients with EDSS progression (≥0.5) expressed a significantly greater CAR compared to HC subjects. RRMS patients with a stable EDSS did not differ from HC subjects. Neither depressive symptoms nor perceived stress ratings were associated with CAR in RRMS patients. In a step-wise regression analysis, EDSS at baseline and CAR were predictive of EDSS at follow-up (R(2) = 67%) for RRMS patients. CONCLUSIONS: Circadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed.