scholarly journals Don’t Go Breaking My Heart: MCMV as a Model for HCMV-Associated Cardiovascular Diseases

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 619
Author(s):  
Cassandra M. Bonavita ◽  
Rhonda D. Cardin

Human Cytomegalovirus (HCMV) is a widespread pathogen that causes lifelong latent infection and is associated with the exacerbation of chronic inflammatory diseases in seropositive individuals. Of particular impact, HCMV infection is known to worsen many cardiovascular diseases including myocarditis, atherosclerosis, hypertension, and transplant vasculopathy. Due to its similarity to HCMV, murine CMV (MCMV) is an appropriate model to understand HCMV-induced pathogenesis in the heart and vasculature. MCMV shares similar sequence homology and recapitulates much of the HCMV pathogenesis, including HCMV-induced cardiovascular diseases. This review provides insight into HCMV-associated cardiovascular diseases and the murine model of MCMV infection, which has been used to study the viral pathogenesis and mechanisms contributing to cardiovascular diseases. Our new functional studies using echocardiography demonstrate tachycardia and hypertrophy in the mouse, similar to HCMV-induced myocarditis in humans. For the first time, we show long term heart dysfunction and that MCMV reactivates from latency in the heart, which raises the intriguing idea that HCMV latency and frequent virus reactivation perturbs long term cardiovascular function.

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Joseph W. Jackson ◽  
Trevor J. Hancock ◽  
Ellen LaPrade ◽  
Pranay Dogra ◽  
Eric R. Gann ◽  
...  

ABSTRACTHuman cytomegalovirus (HCMV) is a betaherpesvirus that is a significant pathogen within newborn and immunocompromised populations. Morbidity associated with HCMV infection is the consequence of viral dissemination. HCMV has evolved to manipulate the host immune system to enhance viral dissemination and ensure long-term survival within the host. The immunomodulatory protein vCXCL-1, a viral chemokine functioning primarily through the CXCR2 chemokine receptor, is hypothesized to attract CXCR2+neutrophils to infection sites, aiding viral dissemination. Neutrophils harbor HCMVin vivo; however, the interaction between vCXCL-1 and the neutrophil has not been evaluatedin vivo. Using the mouse model and mouse cytomegalovirus (MCMV) infection, we show that murine neutrophils harbor and transfer infectious MCMV and that virus replication initiates within this cell type. Utilizing recombinant MCMVs expressing vCXCL-1 from the HCMV strain (Toledo), we demonstrated that vCXCL-1 significantly enhances MCMV dissemination kinetics. Through cellular depletion experiments, we observe that neutrophils impact dissemination but that overall dissemination is largely neutrophil independent. This work adds neutrophils to the list of innate cells (i.e., dendritic and macrophages/monocytes) that contribute to MCMV dissemination but refutes the hypothesis that neutrophils are the primary cell responding to vCXCL-1.IMPORTANCEAn adequatein vivoanalysis of HCMV’s viral chemokine vCXCL-1 has been lacking. Here we generate recombinant MCMVs expressing vCXCL-1 to study vCXCL-1 functionin vivousing MCMV as a surrogate. We demonstrate that vCXCL-1 increases MCMV dissemination kinetics for both primary and secondary dissemination. Additionally, we provide evidence, that the murine neutrophil is largely a bystander in the mouse’s response to vCXCL-1. We confirm the hypothesis that vCXCL-1 is a HCMV virulence factor. Infection of severely immunocompromised mice with MCMVs expressing vCXCL-1 was lethal in more than 50% of infected animals, while all animals infected with parental virus survived during a 12-day period. This work provides needed insights into vCXCL-1 functionin vivo.


2015 ◽  
Vol 12 (1) ◽  
pp. 1-12
Author(s):  
Sarah Hackett

Drawing upon a collection of oral history interviews, this paper offers an insight into entrepreneurial and residential patterns and behaviour amongst Turkish Muslims in the German city of Bremen. The academic literature has traditionally argued that Turkish migrants in Germany have been pushed into self-employment, low-quality housing and segregated neighbourhoods as a result of discrimination, and poor employment and housing opportunities. Yet the interviews reveal the extent to which Bremen’s Turkish Muslims’ performances and experiences have overwhelmingly been the consequences of personal choices and ambitions. For many of the city’s Turkish Muslim entrepreneurs, self-employment had been a long-term objective, and they have succeeded in establishing and running their businesses in the manner they choose with regards to location and clientele, for example. Similarly, interviewees stressed the way in which they were able to shape their housing experiences by opting which districts of the city to live in and by purchasing property. On the whole, they perceive their entrepreneurial and residential practices as both consequences and mediums of success, integration and a loyalty to the city of Bremen. The findings are contextualised within the wider debate regarding the long-term legacy of Germany’s post-war guest-worker system and its position as a “country of immigration”.


1970 ◽  
Vol 19 (1) ◽  
pp. 89-99
Author(s):  
K. Choudhary ◽  
M. Singh ◽  
M. S. Rathore ◽  
N. S. Shekhawat

This long term study demonstrates for the first time that it is possible to propagate embryogenic Vigna trilobata and to subsequently initiate the differentiation of embryos into complete plantlets. Initiation of callus was possible on 2,4-D. Somatic embryos differentiated on modified MS basal nutrient medium with 1.0 mg/l  of 2,4-D and 0.5 mg/l  of Kn. Sustained cell division resulted in globular and heart shape stages of somatic embryos. Transfer of embryos on to a fresh modified MS basal medium with 0.5 mg/l of Kn and 0.5 mg/l of GA3 helped them to attain maturation and germination. However, the propagation of cells, as well as the differentiation of embryos, were inhibited by a continuous application of these growth regulators. For this reason, a long period on medium lacking these growth regulators was necessary before the differentiation of embryos occurred again. The consequences for improving the propagation of embryogenic cultures in Vigna species are discussed. Key words: Pasture  legume, Vigna trilobata, Globular, Heart shape, somatic embryogenesis D.O.I. 10.3329/ptcb.v19i1.4990 Plant Tissue Cult. & Biotech. 19(1): 89-99, 2009 (June)


2017 ◽  
pp. 34-47
Author(s):  
Hoi Le Quoc ◽  
Nam Pham Xuan ◽  
Tuan Nguyen Anh

The study was targeted at developing a methodology for constructing a macroeconomic performance index at a provincial level for the first time in Vietnam based on 4 groups of measurements: (i) Economic indicators; (ii) oriented economic indicators; (iii) socio-economic indicators; and (iv) economic - social – institutional indicators. Applying the methodology to the 2011 - 2015 empirical data of all provinces in Vietnam, the research shows that the socio-economic development strategy implemented by those provinces did not provide balanced outcomes between growth and social objectives, sustainability and inclusiveness. Many provinces focused on economic growth at the cost of structural change, equality and institutional transformation. In contrast, many provinces were successful in improving equality but not growth. Those facts threaten the long-term development objectives of the provinces.


GYNECOLOGY ◽  
2018 ◽  
Vol 20 (6) ◽  
pp. 35-41
Author(s):  
T Yu Pestrikova ◽  
I V Yurasov ◽  
E A Yurasova

Medical, social and economic relevance of inflammatory diseases of the woman's reproductive organs requires a very careful attitude to the diagnosis and treatment of this pathology. The number of patients with genital infections and inflammatory diseases of the pelvic organs can takes the first place in structure of gynecological morbidity, and is 60.4-65.0%, and this fact is not unique to Russia, but all over the world. Incidence rate of inflammatory diseases of the pelvic organs in the first decade of the twenty-first century is increased at 1.4 times in patients who are from 18 to 24 years old and at 1.8 times in patients aged 25-29 years. At the same time, the cost of diagnosis and treatment has increased, reaching 50-60% of the total cost of providing gynecological care for population. The inflammatory diseases of pelvic organs are a collective concept. It includes of various nosological forms. There are numerous contradictions in the views on diagnostic approaches and treatment tactics, the nature of screening and control over the long-term results of treatment, the etiological and pathogenetic significance of various microorganisms found in the genital tract in patients with inflammatory diseases of the pelvic organs. Currently, there are many opinions among specialists about diagnostic approaches and treatment tactics, the type of screening and monitoring the long-term results of treatment, the etiological and pathogenetic role of various microorganisms which can be found in the genital tract in patients with inflammatory diseases. This review presents the results of a modern approach to the diagnosis, management and rehabilitation of patients with inflammatory diseases of the pelvic organs.


Author(s):  
O. D. Golyaeva ◽  
O. V. Kurashev ◽  
S. D. Knyazev ◽  
А. Yu. Bakhotskaya

The main goal of the scientific institution was and remains to improve the assortment of fruit and berry crops for the development of domestic horticulture. Black currant breeding at VNIISPK was started by A.F Tamarova and continued by the doctor of agricultural Sciences T.P.Ogoltsova and doctor of agricultural Sciences S.D. Knyazev. A long-term breeding program has been developed. The main goals of the program are to create black currant cultivars with continuous resistance to diseases, first of all powdery mildew, as wells resistance to pests, i.e. bud mite. As a result of the long-term work, over 40 black currant cultivars have been developed, 14 of them are zoned. Red currant breeding was led by the candidate of agricultural Sciences L.V. Bayanova; since 2001 the work has been continued by the candidate of agricultural Sciences O.D. Golyaeva. ‘Heinemanns Rote Spӓtlese’, the descendant of R. multiflorum Kit., was involved in the red currant breeding for the first time in Russia. On its genetic basis, a series of late maturing cultivars with long and dense racemes was created. At the Institute, in total 21cultivars of red currants have been developed, 13 of them are zoned. At present, red currant cultivars make up 25.5% of the zoned assortment in Russia. The first research on gooseberries was stated by V.P. Semakin and A.F Tamarova; since 1992 the systematic gooseberry breeding has been carried out by the candidate of agricultural Sciences O.V. Kurashev. On the basis of Grossularia robusta, we have created gooseberry forms that are resistant to powdery mildew and leaf spots. These forms are highly productive, weakly thorned, having bush habit suitable for mechanized harvest. The result of breeding activities was the transfer of 6 gooseberry cultivars to State agricultural testing: ‘Solnechny Zaychik’, ‘Nekrasovsky’, ‘Yupiter’, ‘Zemlianichny’, ‘Moryachok’ and ‘Discovery’.


2020 ◽  
pp. 128-138
Author(s):  
A. S. Bik-Bulatov

The article uses little known letters of M. Gorky, many of which were published for the first time in 1997, as well as findings of Samara-based experts in local history to shed light on the writer’s work as editor-in-chief of the Samarskaya Gazeta newspaper in 1895. The researcher introduces hitherto unstudied reminiscences of the journalist D. Linyov (Dalin) about this period, which reference a letter by Gorky, now lost. The paper details a newly discovered episode of Gorky’s professional biography as a journalist: it concerns his campaign against a Samara ‘she-wolf,’ the madam of a local brothel A. Neucheva. Linyov’s reminiscences turn out to be an important and interesting source, offering an insight into the daily grind of the young editor Gorky, providing new evidence of his excellent organizational skills, and describing his moral and social stance. The author presents his work in the context of a recently initiated broader discussion about the need to map out all Russian periodicals for the period until 1917, as well as all research devoted to individual publications.


Author(s):  
Sally Treloyn ◽  
Matthew Dembal Martin ◽  
Rona Goonginda Charles

Repatriation has become almost ubiquitous in ethnomusicological research on Australian Indigenous song. This article provides insights into processes of a repatriation-centered song revitalization project in the Kimberley, northwest Australia. Authored by an ethnomusicologist and two members of the Ngarinyin cultural heritage community, the article provides firsthand accounts of the early phases of a long-term repatriation-centered project referred to locally as the Junba Project. The authors provide a sample of narratives and dialogues that deliver insight into experiences of the work of identifying recordings “in the archive” and cultural negotiation and use of recordings “on Country.” The entanglement of local epistemological frameworks with past and present collection, archival research, repatriation, and dissemination for intergenerational knowledge transmission between spirits, Country, and the living, is explored, showing how recordings move song knowledge from community to archive to community and from generation to generation, and move people in present-day communities. The chapter considers how these “moving songs” allow an interrogation of the fraught endeavor of intercultural collaboration in the pursuit of revitalizing Indigenous song traditions. It positions repatriation as a method that can support intergenerational knowledge transmission and as a method to consider past and present intercultural relationships within research projects and between cultural heritage communities and collecting institutions.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1078
Author(s):  
Fran Krstanović ◽  
William J. Britt ◽  
Stipan Jonjić ◽  
Ilija Brizić

Human cytomegalovirus (HCMV) is a highly prevalent herpesvirus that can cause severe disease in immunocompromised individuals and immunologically immature fetuses and newborns. Most infected newborns are able to resolve the infection without developing sequelae. However, in severe cases, congenital HCMV infection can result in life-threatening pathologies and permanent damage of organ systems that possess a low regenerative capacity. Despite the severity of the problem, HCMV infection of the central nervous system (CNS) remains inadequately characterized to date. Cytomegaloviruses (CMVs) show strict species specificity, limiting the use of HCMV in experimental animals. Infection following intraperitoneal administration of mouse cytomegalovirus (MCMV) into newborn mice efficiently recapitulates many aspects of congenital HCMV infection in CNS. Upon entering the CNS, CMV targets all resident brain cells, consequently leading to the development of widespread histopathology and inflammation. Effector functions from both resident cells and infiltrating immune cells efficiently resolve acute MCMV infection in the CNS. However, host-mediated inflammatory factors can also mediate the development of immunopathologies during CMV infection of the brain. Here, we provide an overview of the cytomegalovirus infection in the brain, local immune response to infection, and mechanisms leading to CNS sequelae.


Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 451
Author(s):  
Marta Kubiak ◽  
Janine Mayer ◽  
Ingo Kampen ◽  
Carsten Schilde ◽  
Rebekka Biedendieck

In biocatalytic processes, the use of free enzymes is often limited due to the lack of long-term stability and reusability. To counteract this, enzymes can be crystallized and then immobilized, generating cross-linked enzyme crystals (CLECs). As mechanical stability and activity of CLECs are crucial, different penicillin G acylases (PGAs) from Gram-positive organisms have proven to be promising candidates for industrial production of new semisynthetic antibiotics, which can be crystallized and cross-linked to characterize the resulting CLECs regarding their mechanical and catalytic properties. The greatest hardness and Young’s modulus determined by indentation with an atomic force microscope were observed for CLECs of Bacillus species FJAT-PGA CLECs (26 MPa/1450 MPa), followed by BmPGA (Priestia megaterium PGA, 23 MPa/1170 MPa) and BtPGA CLECs (Bacillus thermotolerans PGA, 11 MPa/614 MPa). In addition, FJAT- and BtPGA CLECs showed up to 20-fold higher volumetric activities compared to BmPGA CLECs. Correlation to structural characteristics indicated that a high solvent content and low number of cross-linking residues might lead to reduced stability. Furthermore, activity seems to be restricted by small water channels due to severe diffusion limitations. To the best of our knowledge, we show for the first time in this study that the entire process chain for the characterization of diverse industrially relevant enzymes can be performed at the microliter scale to discover the most important relationships and limitations.


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