Various Phases Of Infection Research Articles

Human Adenovirus Gene Expression and Replication Is Regulated through Dynamic Changes in Nucleoprotein Structure throughout Infection.

Human adenovirus (HAdV) is extremely common and can rapidly spread in confined populations such as daycare centers, hospitals, and retirement homes. Although HAdV usually causes only minor illness in otherwise healthy patients, HAdV can cause significant morbidity and mortality in certain populations, such as the very young, very old, or immunocompromised individuals. During infection, the viral DNA undergoes dramatic changes in nucleoprotein structure that promote the rapid expression of viral genes, replication of the DNA, and generation of thousands of new infectious virions-each process requiring a distinct complement of virus and host-encoded proteins. In this review, we summarize our current understanding of the nucleoprotein structure of HAdV DNA during the various phases of infection, the cellular proteins implicated in mediating these changes, and the role of epigenetics in HAdV gene expression and replication.

Detection of Alzheimer’s Disease from MRI scan using Machine Learning An Implementation Paper

Abstract: Alzheimer's disease (AD) is a neurological condition that affects people 65 and older and is a leading cause of dementia. It is crucial to get an accurate and prompt diagnosis of Alzheimer's disease in order to stop the spread of this irreversible infection. This study focuses on using AI to analyze MRI data to detect Alzheimer's disease. The cerebrum's hippocampus area serves as the focal point of the suggested approach. Textural characteristics like entropy, homogeneity, energy, difference, relation, and fluctuations are eliminated from the hippocampus region using the Gray Level Co-Occurrence Matrix (GLCM). The same area that the shape highlighted are removed using the second invariant. Error-back propagation (EBP) is a technique used in artificial neural networks (ANNs) to categorize various phases of infection. The proposed framework has an 86.8% accuracy rate.

Therapeutic efficacy of mebendazole and artemisinin in different phases of trichinellosis: a comparative experimental study.

The present work aimed at studying the efficacy of mebendazole (MBZ) compared to artemisinin (ART) for the treatment of trichinellosis at various phases of infection. Seventy Swiss albino mice were orally infected by 300 Trichinella spiralis (T. spiralis) larvae. Mice were divided into infected untreated control group and infected groups treated with 50 mg kg-1 MBZ and 300 mg kg-1 ART for three and five consecutive days, respectively, at the enteral phase [2-4 days post infection (PI)], invasive phase (10-12 days PI) and encapsulated phase (28-30 days PI). All mice were sacrificed 35-42 days PI. MBZ and ART revealed a significant decrease in mean larval counts and increase of larval per cent reduction (LR %) when treatment was initiated during the enteral phase compared to the other phases. MBZ showed significantly higher LR % (99.7, 83.95 and 89.65%) than ART (80.58, 67.0 and 79.2%) when administered at the three infection phases. Histopathological study showed a decrease in the number of encysted larvae, their surrounding cellular infiltrates and increased regenerative muscles in all treated mice. In conclusion, ART possesses a substantial anthelmintic activity against T. spiralis infection in mice both at the enteral and encapsulated phases, yet, significantly lower than MBZ.

An Observational Study of Intrauterine Vertical Transmission of SARS-CoV-2 in 20 Neonates

Background: Coronavirus Disease 2019 (COVID-19) has become a global pandemic. Neonates have the risk of contracting COVID-19 through intrauterine vertical transmission, which is one of the most serious consequences of infectious diseases. Methods: We enrolled neonates and their mother, who was suffered from COVID-19 during the last trimester. We investigated the presence of SARS-CoV-2, as well as IgG and IgM against the virus in a longitudinal analysis from the labor period to one month after birth. Findings: From February 2 to March 31, 2020, of 20 neonates, 10 neonates and eight neonates had pneumonia and increased lung markings, respectively. At birth, three neonates had positive RT-PCR results of throat swabs, 16 neonates had increased IgG and/or IgM. The mean concentrations of IgG and IgM were mean [SD] 77.7 [28.4] and 11.1 [12.8] ng/mL, respectively. Among nine neonates whose antibody was measured more than once after delivery, one displayed rapidly increased IgM from 1.0 ng/mL at birth to 21.8 ng/mL at 7 days after birth, and 15 showed steadily decreasing IgM. For IgG levels, seven neonates exhibited a slowly decreasing trend after birth and two exhibited a steadily high level. At the birth time, eight neonates were at the acute phase of infection, including five with high or increased IgM and three with positive RT-PCR results. The remaining 12 neonates who had low IgM levels and negative RT-PCR were at the recovery phase. Conclusions: The study identified the presence of intrauterine vertical transmission of SARS-CoV-2, which led to various phases of infection in the neonates at birth time. Funding Statement: This study was supported by the General Program of Health and Family Planning Commission of Hubei Province of China (Grant No. WJ2017M194), the General Program of Natural Science Foundation of Hubei Province of China (Grant No. 2017CFB709), and Natural Science Foundation of Ningbo (2017A610273). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This observational study was reviewed and approved by the Ethics Committee of Wuhan Women and Children's Hospital and followed the Declaration of Helsinki. Written consent was acquired from the guardians of the patients.

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression of molecules that are specifically recognized by NK cell-activating receptors. The main NK cell-activating receptors involved in the recognition and killing of virus-infected cells are NKG2D and DNAM-1. In particular, ligands for DNAM-1 are nectin/nectin-like molecules involved also in mechanisms allowing viral infection. Viruses adopt several immune evasion strategies, including those affecting NK cell-mediated immune surveillance, causing persistent viral infection and the development of virus-associated diseases. The virus’s immune evasion efficacy depends on molecules differently expressed during the various phases of infection. In this review, we overview the molecular strategies adopted by viruses, specifically cytomegalovirus (CMV), human immunodeficiency virus (HIV-1), herpes virus (HSV), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), aiming to evade NK cell-mediated surveillance, with a special focus on the modulation of DNAM-1 activating receptor and its ligands in various phases of the viral life cycle. The increasing understanding of mechanisms involved in the modulation of activating ligands, together with those mediating the viral immune evasion strategies, would provide critical tools leading to design novel NK cell-based immunotherapies aiming at viral infection control, thus improving cure strategies of virus-associated diseases.

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis.

Leishmanioses are chronic parasitic diseases and host responses are associated with pro- or anti-inflammatory cytokines involved, respectively, in the control or exacerbation of infection. The relevance of other inflammatory mediators and stress markers has not been widely studied and there is a need to search for biomarkers to leishmaniasis. In this work, the stress and inflammatory molecules p38 mitogen-activated protein kinase, cyclooxygenase-2, migration inhibitory factor, macrophage inflammatory protein 2, heat shock protein 70 kDa, vascular endothelial factor (VEGF), hypoxia-inducible factors (HIF-1α and HIF-2α), heme oxygenase and galectin-3 expression were assessed immunohistochemically in self-controlled lesions in C57BL/6 mice and severe lesions in Balb/c mice infected with Leishmania amazonensis. The results indicated that the majority of molecules were expressed in the cutaneous lesions of both C57BL/6 and Balb/c mice during various phases of infection, suggesting no obvious correlation between the stress and inflammatory molecule expression and the control/exacerbation of leishmanial lesions. However, the cytokine VEGF was only detected in C57BL/6 footpad lesions and small lesions in Balb/c mice treated with antimonial pentavalent. These findings suggest that VEGF expression could be a predictive factor for murine leishmanial control, a hypothesis that should be tested in human leishmaniosis.

Dynamics of interferon-gamma release assay and cytokine profiles in blood and respiratory tract specimens from mice with tuberculosis and the effect of therapy

There are limitations on diagnostic methods to differentiate between active and latent tuberculosis (TB), and the prediction of latent progression to TB disease is yet complex. Traditionally, tuberculosis-specific host immune response was visualized using the tuberculin skin test. Nowadays, IFN-γ release assays (IGRA) provide a more specific and sensitive tool, by which exposure to Mtb could be determined. However, the merit of IGRA aids in diagnosing active TB is yet unclear. We adapted IGRA for use in mice, and quantifying bead-based flow cytometry techniques were used to assess cytokine profiles during the course of untreated infection and to investigate the value of IGRA and cytokines as biomarkers for therapy response. High variability of IGRA results during progression of active TB infection related to various phases of infection was obtained. However, a significant decrease in IGRA results and in levels of IFN-γ, IL-17, IP-10 or MIG was observed and appeared to be associated with successful therapy. This outcome does not support the value of IGRA to accurately diagnose active TB or to monitor infection progression. However, IGRA proved to be a useful biomarker to monitor therapy success. In addition, different cytokines might serve as biomarkers.

A defect in nir1, a nirA‐like transcription factor, confers morphological abnormalities and loss of pathogenicity in Colletotrichum acutatum

SUMMARY A non-pathogenic mutant of Colletotrichum acutatum, designated Ca5, exhibited epiphytic hyphal growth and did not cause lesions on strawberry plants but grew necrotrophically when inoculated directly onto wounded stolons. In the absence of an external nitrogen source, the mutant exhibited extended germ-tube growth prior to appressorium formation. The deduced product of the impaired gene (nir1) is similar to NirA, an Aspergillus nidulans transcriptional regulator of nitrogen metabolism. Inoculation of leaves with wild-type or Ca5 conidia in the presence of a preferred nitrogen source resulted in massive epiphytic hyphal production, appressorium formation and rapid symptom development. Expression of C. acutatum wild-type nitrate reductase (nit1) and glutamine synthetase (gln1) was induced by nitrate but only nit1 expression was repressed in a rich medium. nit1 transcription increased during the appressorium-production stage, indicating that nitrogen starvation constitutes a cue for the regulation of appressorium development. The presence of nit1 transcript during various phases of infection is indicative of partial nitrogen starvation in planta. cAMP-dependent protein kinase A (PKA) was determined to be a negative regulator of immediate post-germination appressoria formation in the wild-type. As inhibition of PKA activity in the nir1 mutant did not affect appressoria formation, we suggest that NIR1 acts either in parallel or downstream of the PKA pathway. Our results show that nir1 is a pathogenicity determinant and a regulator of pre-infection development under nitrogen-starvation conditions and that nitrogen availability is a significant factor in the pre-penetration phase.

The ratio of cytokine levels in genital herpes during various phases of infection.

The concentrations of cytokines (tumor necrosis factor-alpha and interleukin-10) in cervical scrapes and the percentage of CD4(+)lymphocytes producing interferon-gamma and interleukin-4 in the peripheral blood were measured in women of reproductive age with typical form of genital herpes. The results suggest that genital herpes is a chronic inflammatory process characterized by high levels of proinflammatory cytokines with predominance of T-helper type 1 over T-helper type 2 cytokines.

Analysis of Factors Influencing Kinetics of Herpes Simplex Virus Transcription Utilizing Recombinant Virus

The herpes simplex virus type 1 (HSV-1) transcription program is a regulated cascade in which early and late phases of gene expression are separated by viral DNA replication. While promoters controlling expression of transcripts encoding immediate–early proteins contain virus-specificcis-acting elements, these are in the context of cellular promoter elements, and the promoters controlling expression of other viral transcripts containonlycellularcis-acting elements. We had developed and continue to refine a general method for the production of recombinant viruses in which modified promoters can be inserted into nonessential loci within the viral genome through homologous recombination. This approach has been especially useful in defining the features of model promoters of the various kinetic classes. Our work suggests that class-specific differences in promoter architecture are critical factors in the ability of the cellular transcription machinery to form stable preinitiation complexes at various phases of infection and, thus, mediate kinetic class-specific transcription. Early (β) promoters contain a TATA box and upstream activation elements while sequences downstream of the TATA homology are dispensible for transcription. Late transcripts can be catagorized as either leaky–late (βγ) or strict late (γ) depending on whether they are readily detectable prior to viral DNA replication. Promoters controlling both types are clearly distinct from early ones in that sequences near the transcription start site which resemble consensus mammalian initiator elements are required along with the TATA box and activator elements. Strict late promoters do not contain elements upstream of the TATA box but include what appears to be a class specific element downstream of the transcription start site.

Experimental Schistosoma bovis Infection in Goats: The Inflammatory Response in the Small Intestine and Liver in Various Phases of Infection and Reinfection

In a histopathological study of goats experimentally infected with Schistosoma bovis, the characteristics of the inflammatory response in the small intestine and liver related to tissue egg counts and fecal egg excretion were compared between goats at different time periods of primary infection and of primary infection followed by challenge. At early patency, coinciding with increasing egg excretion, the intestinal lamina propria showed numerous intact schistosome eggs devoid of any inflammatory reaction, whereas egg-associated inflammatory foci in the intestine were significantly few. Later in primary infection and after challenge, intestinal changes were marked by a granulomatous anti-egg response, with only a minor component of eggs lacking inflammatory change, and were consistent with a reduction of egg transfer into the gut wall. Hepatocellular necrosis with eosinophil infiltration was pronounced only during the early patent stage. The results indicate that the early cascade of fecal egg excretion in caprine schistosomosis bovis is aided by a low degree of tissue reactivity to eggs in the intestine. They also lend support to previous findings indicating that an anti-fecundity effect is operative after exposure to challenge in this parasitic infection in goats.

Role of complement in glomerular injury.

The alternative and classical pathway of activation enable the complement system to operate in various phases of infection. Both pathways are tightly controlled by membrane-bound and circulating regulatory proteins. The immediate effects of complement activation comprise the direct lysis of target structures, the generation of proinflammatory molecules and the recruitment of circulating leukocytes. In addition, complement is involved in antigen processing and in the regulation of appropriate immune responses. All functions of complement contribute to the development of glomerular injury. The terminal membrane attack complex acts directly on resident glomerular cells, whereas the earlier components are effective via the recruitment of leukocytes. That the early components are critically involved also in the metabolism and clearance of immune complexes is of special relevance to the pathogenesis of certain glomerular diseases. The exact role of complement components produced locally by resident glomerular cells has yet to be determined.

Analysis of late-blight disease resistance and freezing tolerance in transgenic potato plants expressing sense and antisense genes for an osmotin-like protein

The expression patterns of plant defense genes encoding osmotin and osmotin-like proteins imply a dual function in osmotic stress and plant pathogen defense. We have produced transgenic potato (Solanum commersonii Dun.) plants constitutively expressing sense or antisense RNAs from chimeric gene constructs consisting of the cauliflower mosaic virus 35S promoter and a cDNA (pA13) for an osmotin-like protein. Transgenic potato plants expressing high levels of the pA13 osmotin-like protein showed an increased tolerance to the late-blight fungus Phytophthora infestans at various phases of infection, with a greater resistance at an early phase of fungal infection. There was a decrease in the accumulation of osmotin-like mRNAs and proteins when antisense transformants were challenged by fungal infection, although the antisense transformants did not exhibit any alterations in disease susceptibility. Expression of pA13 sense and antisense RNAs had no effect on the development of freezing tolerance in transgenic plants when assayed under a variety of conditions including treatments with abscisic acid or low temperature. These results provide evidence of antifungal activity for a potato osmotin-like protein against the fungus P. infestans, but do not indicate that pA13 osmotin-like protein is a major determinant of freezing tolerance.

Using two-dimensional gel electrophoresis to study immune response against intracellular bacterial infection.

Principal component analysis was applied to two-dimensional (2-D) gel electrophoresis patterns, obtained in various phases of infection. Untreated controls could be satisfactorily differentiated from patterns after infection on days 3 and 7 whereas day 10 of infection was grouped with the controls. Comparison of host cellular protein patterns could help to classify in vivo developing infection without requiring any so-called immune marker functions. Immunoaffinity separation of infected cells treated with detergent, followed by 2-D electrophoresis of negative as well as positive eluates, did not reveal radiolabeled bacterial protein antigens.

Expression of the human cytomegalovirus UL36–38 immediate early region during permissive infection

We have characterized the expression of human cytomegalovirus immediate early (IE) genes encoding the UL36-38 open reading frames. Single-stranded RNA hybridization probes, transcribed from UL36–38 cDNAs or smaller exon-specific clones, were used in analyses of RNA isolated during various phases of infection in the presence and absence of inhibitors of protein and HCMV DNA synthesis. There are three IE transcripts that arise by the use of alternative promoters and splicing signals. Different patterns of expression are observed for each of the three IE RNAs during permissive infection. Comparison of nucleotide sequences of UL36–38 IE cDNAs with those of the genomic sequence verified the use of polyadenylation and splice signals. An additional abundant early class RNA, totally encoded within the UL36–38 region, was found to be expressed from a different promoter than the IE RNAs. In vitro transcription and translation of the IE cDNAs were used to express the UL36–38 IE proteins. These studies define the structure of the UL36–38 gene products and demonstrate that expression from the region is both qualitatively and temporally complex.

Assembly of Semliki Forest virus nucleocapsid: detection of a precursor in infected cells.

The synthesis of Semliki Forest virus nucleocapsid in infected cells was studied by labelling the virus RNAs with 3H-uridine for different periods at various phases of infection. Short pulses (10 to 20 min) revealed the accumulation of 42S RNA in a ribonucleoprotein which sedimented at about 90S (90S RNP) and contained only small amounts of capsid protein. Only after longer pulses was the labelled 42S RNA found in the virus nucleocapsid, suggesting that the 90S RNP may be its precursor. The life time of the 90S RNP was long in the early phases of infection and short in the late phases, reflecting the increased rate of assembly of the nucleocapsid during infection. The 90S RNP was the only 42S RNA containing RNP found in cells infected with temperature sensitive mutants deficient in nucleocapsid formation or wild type infected cells treated with cycloheximide to inhibit nucleocapsid assembly.