Osteoarthritis in early modern population from Dąbrówki (Podlaskie Province)

The aim of this analized is to evaluate the frequency of osteoarthritis in the early modern population of Dąbrówki (Poland). Evaluation of degenerative joint changes was based on standard methods commonly used in physical anthropology. Three types of changes were studied: osteophytes, porosities, and eburnations. They were analyzed in the shoulder, elbow, wrist, hip, knee, and proximal ankle joints. Osteoarthritic changes were assessed in 24 female, 20 male, and 8 undetermined sex individuals in the Dąbrówki population.In the population from Dąbrówki the highest frequency of degenerative changes was noted in the hip joint, and the lowest in the knee joint. Osteophytes were the predominant type of lesions. The less frequent type was porosity, while polishing of the articular surfaces did not occur. In males, degenerative changes were noted more frequently than in females. Due to the existence of many interpretative limitations (there is no a complete picture of the population from Dąbrówki - skeletal material under exploration; not entirely clear and multifactorial etiology of degenerative joint changes), further analysis of the markers of environmental stress in the population from Dąbrówki is necessary

Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives

Epstein-Barr virus (EBV), the representative of the Herpesviridae family, is a pathogen extensively distributed in the human population. One of its most characteristic features is the capability to establish latent infection in the host. The infected cells serve as a sanctuary for the dormant virus, and therefore their desensitization to apoptotic stimuli is part of the viral strategy for long-term survival. For this reason, EBV encodes a set of anti-apoptotic products. They may increase the viability of infected cells and enhance their resistance to chemotherapy, thereby contributing to the development of EBV-associated diseases, including Burkitt’s lymphoma (BL), Hodgkin’s lymphoma (HL), gastric cancer (GC), nasopharyngeal carcinoma (NPC) and several other malignancies. In this paper, we have described the molecular mechanism of anti-apoptotic actions of a set of EBV proteins. Moreover, we have reviewed the pro-survival role of non-coding viral transcripts: EBV-encoded small RNAs (EBERs) and microRNAs (miRNAs), in EBV-carrying malignant cells. The influence of EBV on the expression, activity and/or intracellular distribution of B-cell lymphoma 2 (Bcl-2) protein family members, has been presented. Finally, we have also discussed therapeutic perspectives of targeting viral anti-apoptotic products or their molecular partners

Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives

Epstein-Barr virus (EBV), the representative of the Herpesviridae family, is a pathogen extensively distributed in the human population. One of its most characteristic features is the capability to establish latent infection in the host. The infected cells serve as a sanctuary for the dormant virus, and therefore their desensitization to apoptotic stimuli is part of the viral strategy for long-term survival. For this reason, EBV encodes a set of anti-apoptotic products. They may increase the viability of infected cells and enhance their resistance to chemotherapy, thereby contributing to the development of EBV-associated diseases, including Burkitt’s lymphoma (BL), Hodgkin’s lymphoma (HL), gastric cancer (GC), nasopharyngeal carcinoma (NPC) and several other malignancies. In this paper, we have described the molecular mechanism of anti-apoptotic actions of a set of EBV proteins. Moreover, we have reviewed the pro-survival role of non-coding viral transcripts: EBV-encoded small RNAs (EBERs) and microRNAs (miRNAs), in EBV-carrying malignant cells. The influence of EBV on the expression, activity and/or intracellular distribution of B-cell lymphoma 2 (Bcl-2) protein family members, has been presented. Finally, we have also discussed therapeutic perspectives of targeting viral anti-apoptotic products or their molecular partners

Changes in the mitochondrial network during ectromelia virus infection of permissive L929 cells

Mitochondria are extremely important organelles in the life of a cell. Recent studies indicate that mitochondria also play a fundamental role in the cellular innate immune mechanisms against viral infections. Moreover, mitochondria are able to alter their shape continuously through fusion and fission. These tightly regulated processes are activated or inhibited under physiological or pathological (e.g. viral infection) conditions to help restore homeostasis. However, many types of viruses, such as orthopoxviruses, have developed various strategies to evade the mitochondrial-mediated antiviral innate immune responses. Moreover, orthopoxviruses exploit the mitochondria for their survival. Such viral activity has been reported during vaccinia virus (VACV) infection. Our study shows that the Moscow strain of ectromelia virus (ECTV-MOS), an orthopoxvirus, alters the mitochondrial network in permissive L929 cells. Upon infection, the branching structure of the mitochondrial network collapses and becomes disorganized followed by destruction of mitochondrial tubules during the late stage of infection. Small, discrete mitochondria co-localize with progeny virions, close to the cell membrane. Furthermore, clustering of mitochondria is observed around viral factories, particularly between the nucleus and viroplasm. Our findings suggest that ECTV-MOS modulates mitochondrial cellular distribution during later stages of the replication cycle, probably enabling viral replication and/or assembly as well as transport of progeny virions inside the cell. However, this requires further investigation

The Role of Bcl-xL Protein in Viral Infections

Bcl-xL represents a family of proteins responsible for the regulation of the intrinsic apoptosis pathway. Due to its anti-apoptotic activity, Bcl-xL co-determines the viability of various virally infected cells. Their survival may determine the effectiveness of viral replication and spread, dynamics of systemic infection, and viral pathogenesis. In this paper, we have reviewed the role of Bcl-xL in the context of host infection by eight different RNA and DNA viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenza A virus (IAV), Epstein-Barr virus (EBV), human T-lymphotropic virus type-1 (HTLV-1), Maraba virus (MRBV), Schmallenberg virus (SBV) and coronavirus (CoV). We have described an influence of viral infection on the intracellular level of Bcl-xL and discussed the impact of Bcl-xL-dependent cell survival control on infection-accompanying pathogenic events such as tissue damage or oncogenesis. We have also presented anti-viral treatment strategies based on the pharmacological regulation of Bcl-xL expression or activity

Disrupting Neurons and Glial Cells Oneness in the Brain—The Possible Causal Role of Herpes Simplex Virus Type 1 (HSV-1) in Alzheimer’s Disease

Current data strongly suggest herpes simplex virus type 1 (HSV-1) infection in the brain as a contributing factor to Alzheimer’s disease (AD). The consequences of HSV-1 brain infection are multilateral, not only are neurons and glial cells damaged, but modifications also occur in their environment, preventing the transmission of signals and fulfillment of homeostatic and immune functions, which can greatly contribute to the development of disease. In this review, we discuss the pathological alterations in the central nervous system (CNS) cells that occur, following HSV-1 infection. We describe the changes in neurons, astrocytes, microglia, and oligodendrocytes related to the production of inflammatory factors, transition of glial cells into a reactive state, oxidative damage, Aβ secretion, tau hyperphosphorylation, apoptosis, and autophagy. Further, HSV-1 infection can affect processes observed during brain aging, and advanced age favors HSV-1 reactivation as well as the entry of the virus into the brain. The host activates pattern recognition receptors (PRRs) for an effective antiviral response during HSV-1 brain infection, which primarily engages type I interferons (IFNs). Future studies regarding the influence of innate immune deficits on AD development, as well as supporting the neuroprotective properties of glial cells, would reveal valuable information on how to harness cytotoxic inflammatory milieu to counter AD initiation and progression

Charakterystyka bakteriologiczna współczesnego drewna zalegającego w glebie na stanowisku archeologicznym w Biskupinie (Polska), w warunkach anoksji - Petrifilmy™ jako alternatywa względem konwencjonalnych podłoży bakteriologicznych

The paper presents results of quantitative and qualitative analyses of the composition of saprophytic and pathogenic microflora colonising contemporary wood of Scots pine (Pinus sylvestris L.) and oak (Quercus sp.), deposited for eight years in peat soil, under anoxia conditions at two measuring stations located at the fortified settlement of the Lusatian culture in Biskupin. Qualitative determinations of bacteria were performed based on the analyses of their cultural, morphological, physiological, and bio-chemical characteristics. Petrifilms™ and conventional bacteriological media were used for quantitative analyses. Bacteria in the examined wood and surrounding soil were identified as belonging to species, including those of the genera Pseudomonas, Clostridium (Cl. butyricum/beierinckii, Cl. perfringens), Bacillus, Corynebacterium, bacteria from the family Enterobacteriaceae, as well as aerobic and anaerobic cellulolytic bacteria. An important correlation between the standard pour plate method and PetrifilmTM was observed. Petrifilms are an effective alternative, in comparison with traditional methods, for the determination of total bacterial counts for wood samples.W pracy przedstawiono wyniki ilościowych i jakościowych analiz składu mikroflory saprofitycznej i patogennej zasiedlającej współczesne drewno sosny zwyczajnej (Pinus sylvestris L.) i dębu (Quercus sp.), zalegające przez okres ośmiu lat w glebie torfowej, w warunkach anoksji, na dwóch stanowiskach pomiarowych umiejscowionych na terenie grodu obronnego kultury łużyckiej w Biskupinie. Oznaczenia jakościowe bakterii przeprowadzono na podstawie analizy ich cech makro- i mikro-morfologicznych, a także fizjologicznych i biochemicznych. Do oznaczeń ilościowych użyto produktów Petrifilm™ i konwencjonalnych pożywek bakteriologicznych. Bakterie w badanym drewnie i otaczającej je glebie zidentyfikowano do gatunków, reprezentujących m.in. rodzaje Pseudomonas, Clostridium (Cl. butyricum/beierinckii, Cl. perfringens), Bacillus, Corynebacterium. Wykryto również bakterie z rodziny Enterobacteriaceae oraz tlenowe i beztlenowe bakterie celulolityczne. Zaobserwowano istotną korelację między wynikami otrzymanymi z wykorzystaniem standardowej metody płytkowej i użyciem techniki wykorzystującej produkty PetrifilmTM. Te ostatnie okazały się być skuteczną alternatywą względem tradycyjnych metod oznaczania całkowitej liczby bakterii w próbkach drewna

Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes

Toll-like receptors (TLRs) sense the presence of pathogen-associated molecular patterns. Nevertheless, the mechanisms modulating TLR-triggered innate immune responses are not yet fully understood. Complex regulatory systems exist to appropriately direct immune responses against foreign or self-nucleic acids, and a critical role of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), endosomal sorting complex required for transportation-0 (ESCRT-0) subunit, has recently been implicated in the endolysosomal transportation of TLR7 and TLR9. We investigated the involvement of Syk, Hrs, and STAM in the regulation of the TLR3 signaling pathway in a murine astrocyte cell line C8-D1A following cell stimulation with a viral dsRNA mimetic. Our data uncover a relationship between TLR3 and ESCRT-0, point out Syk as dsRNA-activated kinase, and suggest the role for Syk in mediating TLR3 signaling in murine astrocytes. We show molecular events that occur shortly after dsRNA stimulation of astrocytes and result in Syk Tyr-342 phosphorylation. Further, TLR3 undergoes proteolytic processing; the resulting TLR3 N-terminal form interacts with Hrs. The knockdown of Syk and Hrs enhances TLR3-mediated antiviral response in the form of IFN-β, IL-6, and CXCL8 secretion. Understanding the role of Syk and Hrs in TLR3 immune responses is of high importance since activation and precise execution of the TLR3 signaling pathway in the brain seem to be particularly significant in mounting an effective antiviral defense. Infection of the brain with herpes simplex type 1 virus may increase the secretion of amyloid-β by neurons and astrocytes and be a causal factor in degenerative diseases such as Alzheimer’s disease. Errors in TLR3 signaling, especially related to the precise regulation of the receptor transportation and degradation, need careful observation as they may disclose foundations to identify novel or sustain known therapeutic targets

Ectromelia Virus Affects Mitochondrial Network Morphology, Distribution, and Physiology in Murine Fibroblasts and Macrophage Cell Line

Mitochondria are multifunctional organelles that participate in numerous processes in response to viral infection, but they are also a target for viruses. The aim of this study was to define subcellular events leading to alterations in mitochondrial morphology and function during infection with ectromelia virus (ECTV). We used two different cell lines and a combination of immunofluorescence techniques, confocal and electron microscopy, and flow cytometry to address subcellular changes following infection. Early in infection of L929 fibroblasts and RAW 264.7 macrophages, mitochondria gathered around viral factories. Later, the mitochondrial network became fragmented, forming punctate mitochondria that co-localized with the progeny virions. ECTV-co-localized mitochondria associated with the cytoskeleton components. Mitochondrial membrane potential, mitochondrial fission–fusion, mitochondrial mass, and generation of reactive oxygen species (ROS) were severely altered later in ECTV infection leading to damage of mitochondria. These results suggest an important role of mitochondria in supplying energy for virus replication and morphogenesis. Presumably, mitochondria participate in transport of viral particles inside and outside of the cell and/or they are a source of membranes for viral envelope formation. We speculate that the observed changes in the mitochondrial network organization and physiology in ECTV-infected cells provide suitable conditions for viral replication and morphogenesis