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17 pages, 24112 KiB  
Article
The Effect of Austempering Temperature on the Matrix Morphology and Thermal Shock Resistance of Compacted Graphite Cast Iron
by Aneta Jakubus, Marek Sławomir Soiński, Grzegorz Stradomski, Maciej Nadolski and Marek Mróz
Materials 2025, 18(10), 2200; https://doi.org/10.3390/ma18102200 - 10 May 2025
Viewed by 724
Abstract
The significance of the matrix morphology of vermicular cast iron for the alloy’s thermal shock resistance was determined. The study included vermicular cast iron subjected to heat treatment in order to obtain an ausferritic matrix. Heat treatment involved austenitization at 960 °C for [...] Read more.
The significance of the matrix morphology of vermicular cast iron for the alloy’s thermal shock resistance was determined. The study included vermicular cast iron subjected to heat treatment in order to obtain an ausferritic matrix. Heat treatment involved austenitization at 960 °C for 90 min, followed by two different austempering variants at 290 °C and 390 °C, each for 90 min. Austempering at 390 °C resulted in a higher content of retained austenite compared to austempering at 290 °C. A test stand was used to determine thermal shock resistance, enabling repeated heating and cooling of the samples. The samples were heated inductively and subsequently cooled in water at a constant temperature of approximately 30 °C. The total length of cracks formed on the wedge-shaped surfaces of the tested samples was adopted as a characteristic value inversely proportional to the material’s thermal shock resistance. The samples heated to 500 °C were subjected to 2000 heating–cooling test cycles. It was found that in as-cast iron, structural changes were minor, whereas in the heat-treated material, changes in the structure were more noticeable. Under the influence of thermal shocks, ausferrite transforms into ferrite with carbides. Among the analyzed materials, the most resistant cast iron was the one austempered at 290 °C. Oxide precipitates were observed near cracks and graphite regions. Full article
(This article belongs to the Special Issue Achievements in Foundry Materials and Technologies)
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54 pages, 9812 KiB  
Review
Australian Cool-Season Pulse Seed-Borne Virus Research: 2. Bean Yellow Mosaic Virus
by Roger A. C. Jones
Viruses 2025, 17(5), 668; https://doi.org/10.3390/v17050668 - 3 May 2025
Viewed by 385
Abstract
Here, research on seed-borne virus diseases of cool-season pulses caused by bean yellow mosaic virus (BYMV) in Australia’s grain cropping regions since the 1940s is reviewed. A historical approach is taken towards all past studies involving the main cool-season pulse crops grown, lupin, [...] Read more.
Here, research on seed-borne virus diseases of cool-season pulses caused by bean yellow mosaic virus (BYMV) in Australia’s grain cropping regions since the 1940s is reviewed. A historical approach is taken towards all past studies involving the main cool-season pulse crops grown, lupin, faba bean, field pea, lentil and chickpea, and the minor ones, narbon bean, vetches and Lathyrus species. The main emphasis adopted is on describing what these studies revealed concerning BYMV biology, epidemiology and management. The field and glasshouse experimentation that enabled the development of effective phytosanitary, cultural and host resistance control strategies, supported by many image illustrations from past investigations, is emphasized. This review commences by providing brief background information and describing past studies on BYMV symptom and sequence variants, and alternative BYMV hosts. Next, as the lupin/BYMV pathosystem has been investigated in much greater depth than any other cool season pulse/BYMV pathosystem combination in Australia, what past studies using it have found is covered considerable detail under a series of nine different sub-headings. Finally, what is known about the less thoroughly investigated cool-season pulse/BYMV pathosystems, especially those involving faba bean, field pea and lentil, is reviewed under seven different sub-headings. Recommendations are provided concerning future research priorities. Full article
(This article belongs to the Special Issue Plant Viruses and Their Vectors: Epidemiology and Control)
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28 pages, 4689 KiB  
Article
Influence of Fatty Acid Desaturase Enzyme-1 Gene (FADS-1) Polymorphism on Serum Polyunsaturated Fatty Acids Levels, Desaturase Enzymes, Lipid Profile, and Glycemic Control Parameters in Newly Diagnosed Diabetic Mellitus Patients
by Hayder Huwais Jarullah and Eman Saadi Saleh
Int. J. Mol. Sci. 2025, 26(9), 4015; https://doi.org/10.3390/ijms26094015 - 24 Apr 2025
Viewed by 1542
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder caused by impaired insulin secretion from pancreatic β-cells and insulin resistance in target tissues. Genome-wide association studies have identified over 50 genetic variants linked to T2DM, including polymorphisms associated with the disease. This [...] Read more.
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder caused by impaired insulin secretion from pancreatic β-cells and insulin resistance in target tissues. Genome-wide association studies have identified over 50 genetic variants linked to T2DM, including polymorphisms associated with the disease. This study investigates the impact of the FADS1 (rs174547) polymorphism in T2DM patients compared to healthy controls and examines serum levels of omega-3 and omega-6 fatty acids, as well as D5D and D6D enzyme levels and activity. This case–control study included 120 participants: 60 newly diagnosed T2DM patients and 60 apparently healthy controls matched for age, sex, and other sociodemographic factors. Polyunsaturated fatty acid (PUFA) levels and desaturase enzyme activities in the n-3 and n-6 pathways were assessed using ELISA and gas chromatography. FADS1 gene polymorphisms were analyzed via Sanger sequencing. Genotype and allele frequencies of FADS1 (rs174547) differed significantly between groups, with higher frequencies of C-containing alleles in T2DM patients. Multivariate analysis revealed a significant association between the C-allele genotype and increased T2DM risk, independent of sociodemographic variables, lipid profile, and inflammatory markers. In conclusion; reduced serum levels of omega-3 and omega-6 fatty acids in T2DM were associated with decreased desaturase enzyme activity. The FADS1 (rs174547) polymorphism is significantly associated with T2DM risk, with the minor allele linked to lower desaturase activity. Full article
(This article belongs to the Special Issue Advances in Molecular Research of Diabetes Mellitus)
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15 pages, 801 KiB  
Review
Syndromic and Non-Syndromic Primary Failure of Tooth Eruption: A Genetic Overview
by Clarissa Modafferi, Elisabetta Tabolacci, Cristina Grippaudo and Pietro Chiurazzi
Genes 2025, 16(2), 147; https://doi.org/10.3390/genes16020147 - 24 Jan 2025
Cited by 1 | Viewed by 1848
Abstract
Primary failure of tooth eruption (PFE) is a rare genetic disorder characterized by the failure of teeth to erupt in the absence of obvious physical obstructions, often resulting in a progressive open bite that is resistant to orthodontic treatment. While PFE can be [...] Read more.
Primary failure of tooth eruption (PFE) is a rare genetic disorder characterized by the failure of teeth to erupt in the absence of obvious physical obstructions, often resulting in a progressive open bite that is resistant to orthodontic treatment. While PFE can be caused by genetic or systemic factors (such as cysts, tumors, and endocrine imbalances), the non-syndromic causes are primarily genetic, with an autosomal dominant inheritance pattern with variable expressivity. Several genes have been closely associated with the non-syndromic PFE form. The PTH1R (parathyroid hormone 1 receptor) is the most commonly PFE-associated gene. Additional genes associated with minor frequency are Transmembrane protein 119 (TMEM119), which reduces the glycolytic efficiency of bone cells, limiting their mineralization capacity and causing bone fragility; Periostin (POSTN), which regulates the extracellular matrix and the bone’s response to mechanical stress; and Lysine (K)-specific methyltransferase 2C (KMT2C), which establishes histone methylation near the Wnt Family Member 5A (WNT5A) gene involved in dental development (odontogenesis). Syndromic forms of PFE are typically associated with complex multisystem disorders, where dental eruption failure is one of the clinical features of the spectrum. These syndromes are often linked to genetic variants that affect ectodermal development, craniofacial patterning, and skeletal growth, leading to abnormal tooth development and eruption patterns. Notable syndromes include GAPO syndrome, ectodermal dysplasia, and cleidocranial dysplasia, each contributing to PFE through distinct molecular mechanisms, such as disruptions in dental structure development, cranial abnormalities, or systemic developmental delays. The main aim of this review is to provide a comprehensive overview of the genetic basis underlying both syndromic and non-syndromic forms of PFE to facilitate precision diagnosis, foster the development of personalized therapeutic strategies, and offer new insights into managing this complex dental anomaly. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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18 pages, 1606 KiB  
Review
Archived HIV-1 Drug Resistance Mutations: Role of Proviral HIV-1 DNA Genotype for the Management of Virological Responder People Living with HIV
by Roberta Campagna, Chiara Nonne, Guido Antonelli and Ombretta Turriziani
Viruses 2024, 16(11), 1697; https://doi.org/10.3390/v16111697 - 30 Oct 2024
Viewed by 2061
Abstract
Despite its effectiveness in controlling plasma viremia, antiretroviral therapy (ART) cannot target proviral DNA, which remains an obstacle to HIV-1 eradication. When treatment is interrupted, the reservoirs can act as a source of viral rebound, highlighting the value of proviral DNA as an [...] Read more.
Despite its effectiveness in controlling plasma viremia, antiretroviral therapy (ART) cannot target proviral DNA, which remains an obstacle to HIV-1 eradication. When treatment is interrupted, the reservoirs can act as a source of viral rebound, highlighting the value of proviral DNA as an additional source of information on an individual’s overall resistance burden. In cases where the viral load is too low for successful HIV-1 RNA genotyping, HIV-1 DNA can help identify resistance mutations in treated individuals. The absence of treatment history, the need to adjust ART despite undetectable viremia, or the presence of LLV further support the use of genotypic resistance tests (GRTs) on HIV-1 DNA. Conventionally, GRTs have been achieved through Sanger sequencing, but the advances in NGS are leading to an increase in its use, allowing the detection of minority variants present in less than 20% of the viral population. The clinical significance of these mutations remains under debate, with interpretations varying based on context. Additionally, proviral DNA is subject to APOBEC3-induced hypermutation, which can lead to defective, nonviable viral genomes, a factor that must be considered when performing GRTs on HIV-1 DNA. Full article
(This article belongs to the Special Issue Antiviral Resistance Mutations)
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20 pages, 3338 KiB  
Article
Next-Generation Sequencing Reveals a High Frequency of HIV-1 Minority Variants and an Expanded Drug Resistance Profile among Individuals on First-Line ART
by Maria Nannyonjo, Jonah Omooja, Daniel Lule Bugembe, Nicholas Bbosa, Sandra Lunkuse, Stella Esther Nabirye, Faridah Nassolo, Hamidah Namagembe, Andrew Abaasa, Anne Kazibwe, Pontiano Kaleebu and Deogratius Ssemwanga
Viruses 2024, 16(9), 1454; https://doi.org/10.3390/v16091454 - 13 Sep 2024
Viewed by 1876
Abstract
We assessed the performance and clinical relevance of Illumina MiSeq next-generation sequencing (NGS) for HIV-1 genotyping compared with Sanger sequencing (SS). We analyzed 167 participants, 45 with virologic failure (VL ≥ 1000 copies/mL), i.e., cases, and 122 time-matched participants with virologic suppression (VL [...] Read more.
We assessed the performance and clinical relevance of Illumina MiSeq next-generation sequencing (NGS) for HIV-1 genotyping compared with Sanger sequencing (SS). We analyzed 167 participants, 45 with virologic failure (VL ≥ 1000 copies/mL), i.e., cases, and 122 time-matched participants with virologic suppression (VL < 1000 copies/mL), i.e., controls, 12 months post-ART initiation. Major surveillance drug resistance mutations (SDRMs) detected by SS were all detectable by NGS. Among cases at 12 months, SS identified SDRMs in 32/45 (71.1%) while NGS identified SDRMs among 35/45 (77.8%), increasing the number of cases with SDRMs by 3/45 (6.7%). Participants identified with, and proportions of major SDRMs increased when NGS was used. NGS vs. SS at endpoint revealed for NNRTIs: 36/45 vs. 33/45; Y181C: 26/45 vs. 24/45; K103N: 9/45 vs. 6/45 participants with SDRMs, respectively. At baseline, NGS revealed major SDRMs in 9/45 (20%) cases without SDRMs by SS. Participant MBL/043, among the nine, the following major SDRMs existed: L90M to PIs, K65R and M184V to NRTIs, and Y181C and K103N to NNRTIs. The SDRMs among the nine increased SDRMs to NRTIs, NNRTIs, and PIs. Only 43/122 (25.7%) of participants had pre-treatment minority SDRMs. Also, 24.4% of the cases vs. 26.2 of controls had minority SDRMs (p = 0.802); minority SDRMs were not associated with virologic failure. NGS agreed with SS in HIV-1 genotyping but detected additional major SDRMs and identified more participants harboring major SDRMs, expanding the HIV DRM profile of this cohort. NGS could improve HIV genotyping to guide treatment decisions for enhancing ART efficacy, a cardinal pre-requisite in the pursuit of the UNAIDS 95-95-95 targets. Full article
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14 pages, 4458 KiB  
Article
Comparison of Different HIV-1 Resistance Interpretation Tools for Next-Generation Sequencing in Italy
by Daniele Armenia, Luca Carioti, Valeria Micheli, Isabella Bon, Tiziano Allice, Celestino Bonura, Bianca Bruzzone, Fiorenza Bracchitta, Francesco Cerutti, Giovanni Maurizio Giammanco, Federica Stefanelli, Maria Addolorata Bonifacio, Ada Bertoli, Marialinda Vatteroni, Gabriele Ibba, Federica Novazzi, Maria Rosaria Lipsi, Nunzia Cuomo, Ilaria Vicenti, Francesca Ceccherini-Silberstein, Barbara Rossetti, Antonia Bezenchek, Francesco Saladini, Maurizio Zazzi and Maria Mercedes Santoroadd Show full author list remove Hide full author list
Viruses 2024, 16(9), 1422; https://doi.org/10.3390/v16091422 - 6 Sep 2024
Cited by 3 | Viewed by 1763
Abstract
Background: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing for HIV genotypic drug resistance testing (GRT). This work evaluated the concordance among different NGS-GRT interpretation tools in a real-life setting. Methods: Routine NGS-GRT data were generated from viral RNA at 11 Italian laboratories [...] Read more.
Background: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing for HIV genotypic drug resistance testing (GRT). This work evaluated the concordance among different NGS-GRT interpretation tools in a real-life setting. Methods: Routine NGS-GRT data were generated from viral RNA at 11 Italian laboratories with the AD4SEQ HIV-1 Solution v2 commercial kit. NGS results were interpreted by the SmartVir system provided by the kit and by two online tools (HyDRA Web and Stanford HIVdb). NGS-GRT was considered valid when the coverage was >100 reads (100×) at each PR/RT/IN resistance-associated position listed in the HIVdb 9.5.1 algorithm. Results: Among 629 NGS-GRT, 75.2%, 74.2%, and 70.9% were valid according to SmartVir, HyDRA Web, and HIVdb. Considering at least two interpretation tools, 463 (73.6%) NGS-GRT had a valid coverage for resistance analyses. The proportion of valid samples was affected by viremia <10,000–1000 copies/mL and non-B subtypes. Mutations at an NGS frequency >10% showed fair concordance among different interpretation tools. Conclusion: This Italian survey on NGS resistance testing suggests that viremia levels and HIV subtype affect NGS-GRT coverage. Within the current routine method for NGS-GRT, only mutations with frequency >10% seem reliably detected across different interpretation tools. Full article
(This article belongs to the Special Issue Antiviral Resistance Mutations)
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21 pages, 16490 KiB  
Article
Integrated Assays of Genome-Wide Association Study, Multi-Omics Co-Localization, and Machine Learning Associated Calcium Signaling Genes with Oilseed Rape Resistance to Sclerotinia sclerotiorum
by Xin-Yao Wang, Chun-Xiu Ren, Qing-Wen Fan, You-Ping Xu, Lu-Wen Wang, Zhou-Lu Mao and Xin-Zhong Cai
Int. J. Mol. Sci. 2024, 25(13), 6932; https://doi.org/10.3390/ijms25136932 - 25 Jun 2024
Cited by 5 | Viewed by 2034
Abstract
Sclerotinia sclerotiorum (Ss) is one of the most devastating fungal pathogens, causing huge yield loss in multiple economically important crops including oilseed rape. Plant resistance to Ss pertains to quantitative disease resistance (QDR) controlled by multiple minor genes. Genome-wide identification of genes involved [...] Read more.
Sclerotinia sclerotiorum (Ss) is one of the most devastating fungal pathogens, causing huge yield loss in multiple economically important crops including oilseed rape. Plant resistance to Ss pertains to quantitative disease resistance (QDR) controlled by multiple minor genes. Genome-wide identification of genes involved in QDR to Ss is yet to be conducted. In this study, we integrated several assays including genome-wide association study (GWAS), multi-omics co-localization, and machine learning prediction to identify, on a genome-wide scale, genes involved in the oilseed rape QDR to Ss. Employing GWAS and multi-omics co-localization, we identified seven resistance-associated loci (RALs) associated with oilseed rape resistance to Ss. Furthermore, we developed a machine learning algorithm and named it Integrative Multi-Omics Analysis and Machine Learning for Target Gene Prediction (iMAP), which integrates multi-omics data to rapidly predict disease resistance-related genes within a broad chromosomal region. Through iMAP based on the identified RALs, we revealed multiple calcium signaling genes related to the QDR to Ss. Population-level analysis of selective sweeps and haplotypes of variants confirmed the positive selection of the predicted calcium signaling genes during evolution. Overall, this study has developed an algorithm that integrates multi-omics data and machine learning methods, providing a powerful tool for predicting target genes associated with specific traits. Furthermore, it makes a basis for further understanding the role and mechanisms of calcium signaling genes in the QDR to Ss. Full article
(This article belongs to the Special Issue New Advances in Plant-Fungal Interactions)
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26 pages, 6696 KiB  
Article
RNA-Seq Bulked Segregant Analysis of an Exotic B. napus ssp. napobrassica (Rutabaga) F2 Population Reveals Novel QTLs for Breeding Clubroot-Resistant Canola
by Zhiyu Yu, Rudolph Fredua-Agyeman, Stephen E. Strelkov and Sheau-Fang Hwang
Int. J. Mol. Sci. 2024, 25(9), 4596; https://doi.org/10.3390/ijms25094596 - 23 Apr 2024
Cited by 2 | Viewed by 1793
Abstract
In this study, a rutabaga (Brassica napus ssp. napobrassica) donor parent FGRA106, which exhibited broad-spectrum resistance to 17 isolates representing 16 pathotypes of Plasmodiophora brassicae, was used in genetic crosses with the susceptible spring-type canola (B. napus ssp. napus [...] Read more.
In this study, a rutabaga (Brassica napus ssp. napobrassica) donor parent FGRA106, which exhibited broad-spectrum resistance to 17 isolates representing 16 pathotypes of Plasmodiophora brassicae, was used in genetic crosses with the susceptible spring-type canola (B. napus ssp. napus) accession FG769. The F2 plants derived from a clubroot-resistant F1 plant were screened against three P. brassicae isolates representing pathotypes 3A, 3D, and 3H. Chi-square (χ2) goodness-of-fit tests indicated that the F2 plants inherited two major clubroot resistance genes from the CR donor FGRA106. The total RNA from plants resistant (R) and susceptible (S) to each pathotype were pooled and subjected to bulked segregant RNA-sequencing (BSR-Seq). The analysis of gene expression profiles identified 431, 67, and 98 differentially expressed genes (DEGs) between the R and S bulks. The variant calling method indicated a total of 12 (7 major + 5 minor) QTLs across seven chromosomes. The seven major QTLs included: BnaA5P3A.CRX1.1, BnaC1P3H.CRX1.2, and BnaC7P3A.CRX1.1 on chromosomes A05, C01, and C07, respectively; and BnaA8P3D.CRX1.1, BnaA8P3D.RCr91.2/BnaA8P3H.RCr91.2, BnaA8P3H.Crr11.3/BnaA8P3D.Crr11.3, and BnaA8P3D.qBrCR381.4 on chromosome A08. A total of 16 of the DEGs were located in the major QTL regions, 13 of which were on chromosome C07. The molecular data suggested that clubroot resistance in FGRA106 may be controlled by major and minor genes on both the A and C genomes, which are deployed in different combinations to confer resistance to the different isolates. This study provides valuable germplasm for the breeding of clubroot-resistant B. napus cultivars in Western Canada. Full article
(This article belongs to the Special Issue Recent Advances in Epigenetics in Plant Research)
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19 pages, 2046 KiB  
Article
Preclinical Antiviral and Safety Profiling of the HBV RNA Destabilizer AB-161
by Angela M. Lam, Ravi R. Dugyala, Muhammed Sheraz, Fei Liu, Emily P. Thi, Ingrid E. Graves, Andrea Cuconati, Holly Micolochick Steuer, Andrzej Ardzinski, Nathan Overholt, Jeremy D. Mason, Dimitar Gotchev, Andrew G. Cole, Troy O. Harasym and Michael J. Sofia
Viruses 2024, 16(3), 323; https://doi.org/10.3390/v16030323 - 21 Feb 2024
Cited by 7 | Viewed by 2877
Abstract
HBV RNA destabilizers are a class of small-molecule compounds that target the noncanonical poly(A) RNA polymerases PAPD5 and PAPD7, resulting in HBV RNA degradation and the suppression of viral proteins including the hepatitis B surface antigen (HBsAg). AB-161 is a next-generation HBV RNA [...] Read more.
HBV RNA destabilizers are a class of small-molecule compounds that target the noncanonical poly(A) RNA polymerases PAPD5 and PAPD7, resulting in HBV RNA degradation and the suppression of viral proteins including the hepatitis B surface antigen (HBsAg). AB-161 is a next-generation HBV RNA destabilizer with potent antiviral activity, inhibiting HBsAg expressed from cccDNA and integrated HBV DNA in HBV cell-based models. AB-161 exhibits broad HBV genotype coverage, maintains activity against variants resistant to nucleoside analogs, and shows additive effects on HBV replication when combined with other classes of HBV inhibitors. In AAV-HBV-transduced mice, the dose-dependent reduction of HBsAg correlated with concentrations of AB-161 in the liver reaching above its effective concentration mediating 90% inhibition (EC90), compared to concentrations in plasma which were substantially below its EC90, indicating that high liver exposure drives antiviral activities. In preclinical 13-week safety studies, minor non-adverse delays in sensory nerve conductance velocity were noted in the high-dose groups in rats and dogs. However, all nerve conduction metrics remained within physiologically normal ranges, with no neurobehavioral or histopathological findings. Despite the improved neurotoxicity profile, microscopic findings associated with male reproductive toxicity were detected in dogs, which subsequently led to the discontinuation of AB-161’s clinical development. Full article
(This article belongs to the Special Issue HBV Transcriptional and Post-transcriptional Regulation)
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17 pages, 313 KiB  
Review
Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review
by Ivana Grgic and Lana Gorenec
Trop. Med. Infect. Dis. 2024, 9(2), 49; https://doi.org/10.3390/tropicalmed9020049 - 15 Feb 2024
Cited by 10 | Viewed by 4663
Abstract
Human cytomegalovirus (HCMV) is a pathogen with high prevalence in the general population that is responsible for high morbidity and mortality in immunocompromised individuals and newborns, while remaining mainly asymptomatic in healthy individuals. The HCMV genome is 236,000 nucleotides long and encodes approximately [...] Read more.
Human cytomegalovirus (HCMV) is a pathogen with high prevalence in the general population that is responsible for high morbidity and mortality in immunocompromised individuals and newborns, while remaining mainly asymptomatic in healthy individuals. The HCMV genome is 236,000 nucleotides long and encodes approximately 200 genes in more than 170 open reading frames, with the highest rate of genetic polymorphisms occurring in the envelope glycoproteins. HCMV infection is treated with antiviral drugs such as ganciclovir, valganciclovir, cidofovir, foscarnet, letermovir and maribavir targeting viral enzymes, DNA polymerase, kinase and the terminase complex. One of the obstacles to successful therapy is the emergence of drug resistance, which can be tested phenotypically or by genotyping using Sanger sequencing, which is a widely available but less sensitive method, or next-generation sequencing performed in samples with a lower viral load to detect minority variants, those representing approximately 1% of the population. The prevalence of drug resistance depends on the population tested, as well as the drug, and ranges from no mutations detected to up to almost 50%. A high prevalence of resistance emphasizes the importance of testing the patient whenever resistance is suspected, which requires the development of more sensitive and rapid tests while also highlighting the need for alternative therapeutic targets, strategies and the development of an effective vaccine. Full article
13 pages, 2962 KiB  
Article
A Fulminant Case of Adenovirus Genotype C108 Infection in a Pediatric Stem Cell Transplant Recipient with x-Linked Lymphoproliferative Syndrome Type 1
by Bradford A. Becken, Daryl M. Lamson, Gabriel Gonzalez, Sachit Patel, Kirsten St. George and Adriana E. Kajon
Viruses 2024, 16(1), 137; https://doi.org/10.3390/v16010137 - 18 Jan 2024
Cited by 3 | Viewed by 2002
Abstract
A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded [...] Read more.
A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded as scheduled, and the patient engrafted on day +19. The patient’s HAdV load in serum continued to rise with resulting hepatic dysfunction, despite ongoing therapy with cidofovir and HAdV specific T-cell infusions. The patient died 6 months after transplantation having never cleared the virus. Next generation whole genome sequencing and sequence data analyses identified an intertypic recombinant HAdV-C P1H2F2 closely related (99.6% similarity) to genotype C108 in the isolates from three blood specimens obtained during the last week of life. Incidentally, the de novo assembly strategy enabled the detection of an adeno-associated virus type 2 (AAV2) genome in the DNA purified from the plasma isolates. Proteotyping analysis revealed minor differences in the predicted amino acid sequences for E1A, E1B 19K, E1B 55K, DNA polymerase, penton base, and fiber. None of the mutations previously described for HAdV-C5 variants resistant to cidofovir were identified. In silico restriction enzyme analysis revealed a distinct Sac I profile for the identified virus, supporting its designation as a C108 variant. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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9 pages, 11133 KiB  
Communication
Effect of Process Pressure on Carbon-Based Thin Films Deposited by Cathodic Arc on Stainless Steel for Bipolar Plates
by Maximilian Steinhorst, Maurizio Giorgio, Teja Roch and Christoph Leyens
Coatings 2023, 13(11), 1962; https://doi.org/10.3390/coatings13111962 - 17 Nov 2023
Cited by 1 | Viewed by 1707
Abstract
In this study, three carbon-based coating variants were deposited onto stainless steel substrates, and the process pressure during the carbon layer deposition was varied. We conducted Raman spectroscopy, transmission electron microscopy, interfacial contact resistance measurements, and potentiodynamic polarization tests to examine the effect [...] Read more.
In this study, three carbon-based coating variants were deposited onto stainless steel substrates, and the process pressure during the carbon layer deposition was varied. We conducted Raman spectroscopy, transmission electron microscopy, interfacial contact resistance measurements, and potentiodynamic polarization tests to examine the effect of the process pressure on the properties of the coatings. The structural characterization revealed that all specimens exhibit a highly sp2-bonded structure. However, some structural differences could also be identified. In the TEM cross-section images of the carbon layer variants, these structural differences could be observed. The carbon layer deposited at 0.98 Pa has some distortions in the mainly perpendicular graphitic structure, which agrees with the Raman results. Almost completely vertically oriented graphitic layers exhibit the 0.1 Pa coating variant with a d-spacing similar to pure graphite. Regarding the contact resistance, the process pressure has only minor influence. All coatings variants have very low resistance values below 3 mΩ cm2, even at a compaction force of 50 N cm−2, which can be attributed to the graphite-like structure. The polarization tests show that the corrosion resistance increases with increasing process pressure. The best coating variant has a corrosion current density of approximately 108 A cm−2 and almost 106 A cm−2 at room temperature and 80 °C, respectively. Full article
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12 pages, 1334 KiB  
Article
HIV Drug Resistance Mutations and Subtype Profiles among Pregnant Women of Ho Chi Minh City, South Vietnam
by Yulia V. Ostankova, Alexandr N. Shchemelev, Huynh Hoang Khanh Thu, Vladimir S. Davydenko, Diana E. Reingardt, Elena N. Serikova, Elena B. Zueva and Areg A. Totolian
Viruses 2023, 15(10), 2008; https://doi.org/10.3390/v15102008 - 27 Sep 2023
Cited by 5 | Viewed by 2136
Abstract
According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population [...] Read more.
According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15–49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71–85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31–72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72–18.10%), and to NNRTIs in 44.26% (95% CI: 31.55–57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection. Full article
(This article belongs to the Special Issue HIV Epidemiology and Drug Resistance)
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Brief Report
HIV-1 Low-Frequency Variants Identified in Antiretroviral-Naïve Subjects with Virologic Failure after 12 Months of Follow-Up in Panama
by Ambar Moreno, Claudia González, Jessica Góndola, Oris Chavarría, Alma Ortiz, Jorge Castillo, Juan Castillo Mewa, Juan Miguel Pascale and Alexander Augusto Martínez
Infect. Dis. Rep. 2023, 15(4), 436-444; https://doi.org/10.3390/idr15040044 - 1 Aug 2023
Cited by 1 | Viewed by 2273
Abstract
Low-frequency mutations associated with drug resistance have been related to virologic failure in subjects with no history of pre-treatment and recent HIV diagnosis. In total, 78 antiretroviral treatment (ART)-naïve subjects with a recent HIV diagnosis were selected and followed by CD4+ T lymphocytes [...] Read more.
Low-frequency mutations associated with drug resistance have been related to virologic failure in subjects with no history of pre-treatment and recent HIV diagnosis. In total, 78 antiretroviral treatment (ART)-naïve subjects with a recent HIV diagnosis were selected and followed by CD4+ T lymphocytes and viral load tests to detect virologic failure. We sequenced the basal samples retrospectively using next-generation sequencing (NGS), looking for low-frequency mutations that had not been detected before using the Sanger sequencing method (SSM) and describing the response to ART. Twenty-two subjects developed virologic failure (VF), and thirteen of them had at least one drug-resistance mutation associated with Reverse Transcriptase Inhibitors (RTI) and Protease Inhibitors (PIs) at frequency levels ≤ 1%, not detected previously in their basal genotyping test. No resistance mutations were observed to Integrase Strand Transfer Inhibitors (INSTIs). We identified a possible cause of VF in ART-naïve subjects with low-frequency mutations detected. To our knowledge, this is the first evaluation of pre-existing drug resistance for HIV-1 minority variants carried out on ART-naïve people living with HIV/AIDS (PLWHA) by analyzing the HIV-1 pol gene using NGS in the country. Full article
(This article belongs to the Section HIV-AIDS)
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