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IScience Jun 2024The intact proviral DNA assay (IPDA) based on droplet digital PCR was developed to identify intact proviral DNA and quantify HIV-1 latency reservoirs in patients...
The intact proviral DNA assay (IPDA) based on droplet digital PCR was developed to identify intact proviral DNA and quantify HIV-1 latency reservoirs in patients infected with HIV-1. However, the genetic characteristics of different HIV-1 subtypes are non-consistent due to their high mutation and recombination rates. Here, we identified that the IPDA based on the sequences features of an HIV-1 subtype could not effectively detect different HIV-1 subtypes due to the high diversity of HIV-1. Furthermore, we demonstrated that mutations in gene outside the probe binding site affect the detection efficiency of IPDA. Since mutations in gene outside the probe binding site may also lead to the formation of stop codons, thereby preventing the formation of viruses and ultimately overestimating the number of HIV-1 latency reservoirs, it is important to address the effect of mutations on the IPDA.
PubMed: 38812543
DOI: 10.1016/j.isci.2024.109941 -
Nature Communications May 2024The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has...
The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.
Topics: Oryza; Haplotypes; Quantitative Trait Loci; Genome, Plant; Chromosomes, Plant; Plant Breeding; Disease Resistance; Plant Diseases; Chromosome Mapping; Stress, Physiological; Genes, Plant
PubMed: 38811581
DOI: 10.1038/s41467-024-48845-6 -
Frontiers in Cellular and Infection... 2024is a uniquely adapted human pathogen and the etiological agent of gonorrhea, a sexually transmitted disease. has developed numerous mechanisms to avoid and actively...
is a uniquely adapted human pathogen and the etiological agent of gonorrhea, a sexually transmitted disease. has developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses. successfully colonizes and establishes topologically distinct colonies in human macrophages and avoids phagocytic killing. During colonization, manipulates the actin cytoskeleton to invade and create an intracellular niche supportive of bacterial replication. The cellular reservoir(s) supporting bacterial replication and persistence in gonorrhea infections are poorly defined. The manner in which gonococci colonize macrophages points to this innate immune phagocyte as a strong candidate for a cellular niche during natural infection. Here we investigate whether nutrients availability and immunological polarization alter macrophage colonization by . Differentiation of macrophages in pro-inflammatory (M1-like) and tolerogenic (M2-like) phenotypes prior to infection reveals that can invade macrophages in all activation states, albeit with lower efficiency in M1-like macrophages. These results suggest that during natural infection, bacteria could invade and grow within macrophages regardless of the nutrients availability and the macrophage immune activation status.
Topics: Neisseria gonorrhoeae; Macrophages; Humans; Nutrients; Gonorrhea; Macrophage Activation; Host-Pathogen Interactions
PubMed: 38808065
DOI: 10.3389/fcimb.2024.1384611 -
Leprosy reactions: Unraveling immunological mechanisms underlying tissue damage in leprosy patients.Pathogens and Disease Feb 2024Leprosy is a chronic granulomatous infectious and disabling disease caused by two mycobacteria, Mycobacterium leprae and Mycobacterium lepromatosis. Acute inflammatory... (Review)
Review
Leprosy is a chronic granulomatous infectious and disabling disease caused by two mycobacteria, Mycobacterium leprae and Mycobacterium lepromatosis. Acute inflammatory responses, known as leprosy reactions, are significant contributors to disabilities. Three types of leprosy reactions have been identified based on excessive cytokine release (e.g. type 1) or the accumulation of immune complexes in tissues inducing multiorgan damage (e.g. types 2 and 3). The type of leprosy reaction has implications on treatment and management strategies, yet are not well understood by health workers caring for leprosy patients. We attempt to describe the immunologic mechanisms behind the different leprosy reactions and the rationale for tailoring clinical treatment and management to the particular type of leprosy reaction based on the underlying immunologic situation.
Topics: Humans; Leprosy; Mycobacterium leprae; Cytokines
PubMed: 38806255
DOI: 10.1093/femspd/ftae013 -
PLoS Pathogens May 2024The common liver fluke (Fasciola hepatica) causes the disease fasciolosis, which results in considerable losses within the global agri-food industry. There is a...
The common liver fluke (Fasciola hepatica) causes the disease fasciolosis, which results in considerable losses within the global agri-food industry. There is a shortfall in the drugs that are effective against both the adult and juvenile life stages within the mammalian host, such that new drug targets are needed. Over the last decade the stem cells of parasitic flatworms have emerged as reservoirs of putative novel targets due to their role in development and homeostasis, including at host-parasite interfaces. Here, we investigate and characterise the proliferating cells that underpin development in F. hepatica. We provide evidence that these cells are capable of self-renewal, differentiation, and are sensitive to ionising radiation- all attributes of neoblasts in other flatworms. Changes in cell proliferation were also noted during the early stages of in vitro juvenile growth/development (around four to seven days post excystment), which coincided with a marked reduction in the nuclear area of proliferating cells. Furthermore, we generated transcriptomes from worms following irradiation-based ablation of neoblasts, identifying 124 significantly downregulated transcripts, including known stem cell markers such as fgfrA and plk1. Sixty-eight of these had homologues associated with neoblast-like cells in Schistosoma mansoni. Finally, RNA interference mediated knockdown of histone h2b (a marker of proliferating cells), ablated neoblast-like cells and impaired worm development in vitro. In summary, this work demonstrates that the proliferating cells of F. hepatica are equivalent to neoblasts of other flatworm species and demonstrate that they may serve as attractive targets for novel anthelmintics.
Topics: Animals; Fasciola hepatica; Stem Cells; Fascioliasis; Cell Proliferation; Cell Differentiation
PubMed: 38805551
DOI: 10.1371/journal.ppat.1011903 -
Journal of Neuroinflammation May 2024Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders... (Review)
Review
Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.
Topics: Brain Injuries, Traumatic; Humans; Animals; Meninges; Neuroinflammatory Diseases; Neuroimmunomodulation
PubMed: 38802931
DOI: 10.1186/s12974-024-03122-7 -
Scientific Reports May 2024The co-existence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH) has raised interest in identifying shared molecular mechanisms and...
The co-existence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH) has raised interest in identifying shared molecular mechanisms and potential therapeutic targets. However, the relationship between these two diseases remains unclear and effective medical treatments are still lacking. Through the bioinformatics analysis in this study, 116 shared differentially expressed genes (SDEGs) were identified between IBD and NASH datasets. GO and KEGG pathway analyses revealed significant involvement of SDEGs in apoptotic processes, cell death, defense response, cytokine and chemokine activity, and signaling pathways. Furthermore, weighted gene co-expression network analysis (WGCNA) identified five shared signature genes associated specifically with IBD and NASH, they were CXCL9, GIMAP2, ADAMTS5, GRAP, and PRF1. These five genes represented potential diagnostic biomarkers for distinguishing patients with diseases from healthy individuals by using two classifier algorithms and were positively related to autophagy, ferroptosis, angiogenesis, and immune checkpoint factors in the two diseases. Additionally, single-cell analysis of IBD and NASH samples highlighted the expression of regulatory genes in various immune cell subtypes, emphasizing their significance in disease pathogenesis. Our work elucidated the shared signature genes and regulatory mechanisms of IBD and NASH, which could provide new potential therapies for patients with IBD and NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Inflammatory Bowel Diseases; Computational Biology; Gene Regulatory Networks; Gene Expression Profiling; Chemokine CXCL9; Biomarkers; Transcriptome; Gene Expression Regulation
PubMed: 38802459
DOI: 10.1038/s41598-024-62310-w -
Nature Communications May 2024Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and...
Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.
Topics: Humans; Male; Virus Shedding; Antibodies, Viral; Prospective Studies; Adult; Monkeypox virus; Mpox (monkeypox); Saliva; HIV Infections; Antibodies, Neutralizing; Middle Aged; Longitudinal Studies; DNA, Viral; Oropharynx; Coinfection; Viral Load; Fomites
PubMed: 38802350
DOI: 10.1038/s41467-024-48754-8 -
Parasite Epidemiology and Control May 2024Cystic echinococcosis (CE) is a major medical and veterinary concern in the world. It is one of the significant diseases in livestock farming communities managed under...
Epidemiological study on bovine cystic echinococcosis: Abattoir survey, cyst characterization and its economic impact at Mekaneyesuse municipality abattoir, Northwest Ethiopia.
Cystic echinococcosis (CE) is a major medical and veterinary concern in the world. It is one of the significant diseases in livestock farming communities managed under extensive grazing system like Ethiopia. Domestic intermediate hosts are an important reservoir for the disease spread. A cross-sectional study was conducted to determine the occurrence and economic losses associated with CE in cattle slaughtered at Mekaneyesuse Municipality abattoir, South Gondor zone of Amhara Region, North West Ethiopia. Ante-mortem inspection, postmortem examinations of organs, hydatid cyst characterization and financial loss estimations were conducted. The study was conducted on 384 cattle. The involvement of different organs was as follows: lungs (46.09%), liver (45.22%), heart (6.09%), and kidneys (2.6%). Out of the total of 115 cysts observed, small cysts constituted 57.39%, medium-sized were 34.78%, and large cysts accounted for 7.83%. Of these 115 cysts, 53.9% were fertile which included both viable (29%) and non-viable (71%) cysts. Furthermore, 46.1% cysts were non fertile, 62.3% were sterile and 37.7% were calcified. Based on the origin of animal, the prevalence of hydatid cysts was recorded to be 31.25%, 24%, 22.05% and 14.25% in Tachgayent, Semada, Andabet and Estie district, respectively. Higher cyst occurrence was observed in animals with poor body condition (51.56%) followed by medium (13.7%) and good body condition scores (8.25%). The total annual economic loss due to the direct condemnation of organs and indirect losses were estimated to be 851,252.68 ETB ($16,061.06). This study revealed that CE is economically important disease at Mekaneyesuse, South Gondar Zone, Amhara Region, Northwest Ethiopia. A more comprehensive investigation is required on prevalence and genotyping of cysts is important also to identify and estimate the relative contribution of each species or genotype to the disease in this area. Moreover, efforts to enhance public awareness in the area should also be pursued.
PubMed: 38800636
DOI: 10.1016/j.parepi.2024.e00355 -
MedRxiv : the Preprint Server For... May 2024Chickens are an important source of animal protein, nutrition, and income in many low- and middle-income countries (LMICs). They are also a major reservoir of...
BACKGROUND
Chickens are an important source of animal protein, nutrition, and income in many low- and middle-income countries (LMICs). They are also a major reservoir of enteropathogens that contribute to the burden of illnesses among children. Food systems present a risk for transmission of enteropathogens from poultry to humans, but there is a lack of population-level data on the pattern of purchase, ownership, and consumption of live chickens and their products in LMICs to better characterize that risk.
METHODS
To assess chicken purchase, ownership, and consumption practices, we conducted a population-based survey using a structured questionnaire in Maputo, Mozambique in 2021. Multi-stage cluster sampling was used to obtain a representative sample of households in our study area. To minimize sampling bias and ensure a representative sample, we applied survey weighting using district-level population data and estimated weighted population-level values.
RESULTS
Heads of 570 households in Maputo completed our survey. Approximately half of these households purchased broiler chicken meat (weighted percentage of households: 44.8%) and eggs (46.5%) in the previous week of the survey date, while indigenous chicken meat was less popular (1,950, 1.1%). The most common source of chicken products was corner stores (i.e., small convenience shops on streets), followed by wet markets. Live chickens were raised by 15.6% of households, and chicken feces were observed on the floor or ground at the majority of these households during house visits.
DISCUSSION
Our findings suggest that poultry provides a major source of animal protein in this setting. With the predicted growth of poultry farming in LMICs in the coming decades, ensuring food safety at the primary sources of chicken products (corner stores and wet markets) in urban areas will be critical to mitigate health risks.
PubMed: 38798325
DOI: 10.1101/2024.05.14.24307337