SEARCH · PubMed Health

Results for “Pathogen diversity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2006

Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.

Natural killer T (NKT) cells recognize glycosphingolipids presented by CD1d molecules and have been linked to defense against microbial infections. Previously defined foreign glycosphingolipids recognized by NKT cells are uniquely found in nonpathogenic sphingomonas bacteria. Here we show that mouse and human NKT cells also recognized glycolipids, specifically a diacylglycerol, from Borrelia burgdorferi, which causes Lyme disease. The B. burgdorferi-derived, glycolipid-induced NKT cell proliferation and cytokine production and the antigenic potency of this glycolipid was dependent on acyl chain length and saturation. These data indicate that NKT cells recognize categories of glycolipids beyond those in sphingomonas and suggest that NKT cell responses driven by T cell receptor-mediated glycolipid recognition may provide protection against diverse pathogens.

Animals↗

PubMed2026

Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies.

Bronchiectasis is a heterogeneous chronic airway disease primarily driven by persistent infection, microbial dysbiosis and dysregulated host immunity. While culture-based microbiology has historically informed clinical management, advances in high-throughput sequencing and multi-omic technologies have transformed our understanding of the airway ecosystem, revealing that disease activity is shaped not only by individual pathogens, but by complex and dynamic host-microbe interactions. Despite the breadth of descriptive microbiome data, translation into clinically actionable diagnostics or therapies has been limited. Importantly, cross-sectional correlations between microbiota and inflammation do not establish cause and effect, underscoring the need to embed host-microbiome profiling within both longitudinal and interventional therapeutic trials. In this review, we critically appraise current microbial and host multi-omics research in bronchiectasis, integrating microbiome studies with host inflammatory, proteomic and immunophenotyping data. We highlight themes emerging across cohorts, including low microbial diversity, pathogen dominance, loss of commensal networks and neutrophil-driven inflammation, and discuss how these features align with biological endotypes associated with exacerbations and treatment response. Drawing on lessons from host-directed therapeutic successes, we examine translational roadblocks limiting microbiome-guided care. We further review emerging microbiome-modulating strategies such as pathogen-specific biologics, bacteriophage therapy, live biotherapeutic products, biofilm-targeting adjuncts and precision antibiotic stewardship. Finally, we propose a roadmap toward microbiome-informed precision medicine through harmonised methodologies, integration of host and microbial biomarkers into clinical trials, and embedding multi-omics pipelines within large international registries. Collectively, these advances have the potential to shift bronchiectasis research and clinical management towards rationally designed, precision medicine-driven therapeutic strategies.

Humans↗

PubMed2026

The Hidden Diversity of Benyviridae and their Polymyxa Vectors: A Comparative Analysis.

The Benyviridae family encompasses multipartite soil-borne phytoviruses characterized by rod-shaped virions and positive single-stranded RNA genomes. The family is mostly known for its type species, the beet necrotic yellow vein virus, the causal agent of rhizomania on sugar beet. However, the recent description of candidate Benyviridae species and "beny-like" sequences suggests a far greater diversity than previously recognized. Also, their increasing relevance in agriculture has drawn attention to this family of viruses. In this review, we provide a comparative analysis of Benyviridae viruses, including newly identified emerging relatives. We highlight recent advances in understanding their diversity, pathogenicity, and interaction with plant hosts and their plasmodiophorid vectors, Polymyxa spp., that remain poorly characterized. Finally, we identify critical knowledge gaps and exciting opportunities-particularly in vector biology, host interactions, and the ecological dynamics of viral spread-that will shape the research ahead.

Plant Viruses↗

PubMed2001

Bacterial and viral etiology of acute otitis media in Chilean children.

BACKGROUND: Acute otitis media (AOM) is a main cause for antimicrobial prescription in Latin America. Pathogen diversity in different geographic regions underscores the need for updated knowledge on AOM microbiology. AIM: To prospectively determine the role of bacteria and viruses in Chilean children with AOM. METHODS: Between July, 1998, and June, 1999, children >3 months with a presumptive diagnosis of AOM were referred to the study ear, nose and throat physician. Middle ear fluid and nasopharyngeal aspirates were obtained from children with confirmed AOM and processed for common bacteria, Mycoplasma pneumoniae, Chlamydia pneumoniae and viruses. Antimicrobial susceptibility patterns and serotypes of Streptococcus pneumoniae strains were determined. RESULTS: An ear, nose and throat physician confirmed diagnoses for 222 (42%) of 529 children referred with diagnosis of AOM, and 170 children met eligibility criteria for the study. One or more pathogens were detected in 140 of 170 (82%) children. Predominant bacteria were S. pneumoniae (37%), Haemophilus influenzae (24%) and Streptococcus pyogenes (13%). M. catarrhalis was detected in 2 children, C. pneumoniae was found in 1 and M. pneumoniae was not detected. Viruses were detected in 22 children (13%) from nasopharyngeal aspirates, and in 6 of them the same virus was detected in middle ear fluid. Penicillin-resistant (intermediate and high) S. pneumoniae represented 40% of isolates and 10% of H. influenzae were beta-lactamase producers. All 10 penicillin-resistant S. pneumoniae strains were resistant to cefuroxime. Eighteen S. pneumoniae serotypes were detected and 19F was associated with high level penicillin resistance. CONCLUSION: This study can impact local management of AOM, and it should encourage continuous surveillance of AOM microbiology in Chile and other developing countries.

Acute Disease↗

PubMed1993

Selection of rabbit CD4- CD8- T cell receptor-gamma/delta cells by in vitro transformation with human T lymphotropic virus-I.

In vitro transformation of rabbit peripheral blood mononuclear cells (PBMC) with human T lymphotropic virus-I (HTLV)-infected human or rabbit cells resulted in CD4- CD8- cell lines, some of which caused acute leukemia when injected into rabbits. Structural analyses of the proviruses from cell lines with diverse pathogenic effects provided no clear correlation with lethality. The rabbit lines were provisionally designated T cells because they express interleukin 2R (IL-2R) and CD5 and lack surface immunoglobulin, but none express functional T cell receptor (TCR) alpha or beta transcripts. A more detailed characterization of the HTLV-I-infected cells was required to determine cell lineage and its potential influence on pathogenic consequences. Probes for rabbit TCR gamma and delta genes were derived and used to detect gamma and delta TCR RNA transcripts, identifying the in vitro transformed lines as gamma/delta T cells. CD4+ and CD8+ lines were derived from PBMC of HTLV-I-infected rabbits and CD4+ TCR-alpha/beta HTLV-I lines were derived from rabbit thymus, eliminating the possibility that the HTLV-I isolates used here transform only CD4- CD8- TCR-gamma/delta cells. The percentage of gamma/delta cells in rabbit PBMC is relatively high (23% in adult rabbits); this with diminution of CD4+ and CD8+ cells in IL-2-supplemented PBMC or thymocyte cultures may account for selection of rabbit HTLV-I-infected gamma/delta T cell lines in vitro. The availability of well-characterized T cell lines with diverse in vivo effects in the rabbit HTLV-I disease model allows evaluation of roles played by cell type in HTLV-I-mediated disease.

Animals↗

PubMed1996

Two pathogenicity islands in uropathogenic Escherichia coli J96: cosmid cloning and sample sequencing.

Many of the virulence genes of pathogenic strains of Escherichia coli are carried in large multigene chromosomal segments called pathogenicity islands (PAIs) that are absent from normal fecal and laboratory K-12 strains of this bacterium. We are studying PAIs in order to better understand factors that govern virulence and to assess how such DNA segments are gained or lost during evolution. The isolation and sample sequencing of a set of 11 cosmid clones that cover all of one and much of a second large PAI in the uropathogenic E. coli J96 are described. These PAIs were mapped to the 64- and 94-min regions of the E. coli K-12 chromosome, which differ from the locations of three PAIs identified in other pathogenic E. coli strains. Analysis of the junction sequences with E. coli K-12-like DNAs showed that the insert at 94 min is within the 3' end of a phenylalanine tRNA gene, pheR, and is flanked by a 135-bp imperfect direct repeat. Analysis of the one junction recovered from the insert at 64 min indicated that it lies near another tRNA gene, pheV. To identify possible genes unique to these PAIs, 100 independent subclones of the cosmids were made by PstI digestion and ligation into a pBS+ plasmid and used in one-pass sample DNA sequencing from primer binding sites at the cloning site in the vector DNA. Database searches of the J96 PAI-specific sequences identified numerous instances in which the cloned DNAs shared significant sequence similarities to adhesins, toxins, and other virulence determinants of diverse pathogens. Several likely insertion sequence elements (IS100, IS630, and IS911) and conjugative R1 plasmid and P4 phage genes were also found. We propose that such mobile genetic elements may have facilitated the spread of virulence determinants within PAIs among bacteria.

Base Sequence↗

PubMed2003

New biochip technology for label-free detection of pathogens and their toxins.

microSERS is a new biochip technology that uses surface-enhanced Raman scattering (SERS) microscopy for label-free transduction. The biochip itself comprises pixels of capture biomolecules immobilized on a SERS-active metal surface. Once the biochip has been exposed to the sample and the capture biomolecules have selectively bound their ligands, a Raman microscope is used to collect SERS fingerprints from the pixels on the chip. SERS, like other whole-organism fingerprinting techniques, is very specific. Our initial studies have shown that the Gram-positive Listeria and Gram-negative Legionella bacteria, Bacillus spores and Cryptosporidium oocysts can often be identified at the subspecies/strain level on the basis of SERS fingerprints collected from single organisms. Therefore, pathogens can be individually identified by microSERS, even when organisms that cross-react with the capture biomolecules are present in a sample. Moreover, the SERS fingerprint reflects the physiological state of a bacterial cell, e.g., when pathogenic Listeria and Legionella were cultured under conditions known to affect virulence, their SERS fingerprints changed significantly. Similarly, nonviable (e.g., heat- or UV-killed) microorganisms could be differentiated from their viable counterparts by SERS fingerprinting. Finally, microSERS is also capable of the sensitive and highly specific detection of toxins. Toxins that comprised as little as 0.02% by weight of the biomolecule-toxin complex produced strong, unique fingerprints when spectra collected from the complexes were subtracted from the spectra of the uncomplexed biomolecules. For example, aflatoxins B(1) and G(1) could be detected and individually identified when biochips bearing pixels of antibody or enzyme capture biomolecules were incubated in samples containing one or both aflatoxins, and the spectra were then collected for 20 s from an area of the biomolecule pixel approximately 1 microm in diameter. In the future, we plan to investigate the use of hyperspectral imaging Raman microscopy for collecting fingerprints from all the pixels on the biochip, individually yet simultaneously, to enable the rapid detection of diverse pathogens and their toxins in a sample, using a single biochip.

Aflatoxins↗

PubMed2026

Mannheimia haemolytica strain-level diversity in cattle populations.

High-resolution genomic characterization is essential for understanding diversity, pathogenicity, and transmission dynamics of bacterial pathogens. Mannheimia haemolytica (Mh) is the most consequential bacterial agent associated with bovine respiratory disease (BRD) in cattle, as a leading cause of morbidity, mortality, and antimicrobial use. Historically, BRD pathogens, including Mh, have been studied using culture or PCR approaches that provided limited ability to characterize fine-scale genomic variation across communities. Here, we evaluated target-enriched (TE) shotgun sequencing, a culture-independent method capable of strain-level resolution within metagenomic data, for detecting and characterizing Mh in comparison with qPCR and 16S rRNA gene sequencing. Nasal swabs (10 individual and 2 composited DNA samples per pen) and environmental samples (three ropes hung on pen rails and three water bowl swabs per pen) were collected from four pens in each of five distinct cattle populations. DNA was extracted for TE sequencing to identify Mh at both species and genomic sequence variant (GSV) levels, and to characterize antimicrobial resistance genes across the bacterial communities. qPCR was performed to quantify Mh genome copies, and 16S rRNA gene sequencing was used to assess the broader respiratory microbiome. TE sequencing identified Mh in 100% of TE-tested samples and classified multiple GSVs in all but 3 of 121 samples. GSV profiles clustered within housing groups and varied across cattle populations, indicating structured strain-level diversity. In contrast, Mannheimia spp. were detected in only 47.7% of samples by 16S rRNA sequencing. These findings demonstrate that TE sequencing enables sensitive, strain-level characterization of Mh in cattle and environmental samples and reveals substantial within-population genomic diversity not captured by conventional approaches.IMPORTANCETarget-enriched shotgun sequencing enabled sensitive, strain-level detection of Mannheimia haemolytica (Mh), revealing multiple co-circulating genomic sequence variants (GSVs) within and among cattle groups. This demonstrates greater genetic variability of Mh populations in beef cattle than has been previously recognized. The clustering of GSVs within housing groups, together with the overlap between respiratory and environmental samples, is consistent with the hypothesis that contagious transmission contributes to Mh ecology. These results highlight the potential utility of composite nasal swab and environmental samples for future studies evaluating relationships between Mh genomic variation and disease risk.

Animals↗

PubMed2002

A defective, rearranged Epstein-Barr virus genome in EBER-negative and EBER-positive Hodgkin's disease.

A ubiquitous herpesvirus that establishes life-long infection, the Epstein-Barr virus (EBV) has yielded little insight into how a single agent in general accord with its host can produce diverse pathologies ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's lymphoma. Its pathogenesis is further confounded by the less than total association of virus with histologically similar tumors. In other viral systems, defective (interfering) viral genomes are known to modulate outcome of infection, with either ameliorating or intensifying effects on disease processes initiated by prototype strains. To ascertain whether defective EBV genomes are present in HD, we examined paraffin-embedded tissue from 56 HD cases whose EBV status was first determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs). Using both standard polymerase chain reaction (PCR) and PCR in situ hybridization, we successfully amplified sequences that span abnormally juxtaposed BamHI W and Z fragments characteristic of defective heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of 24 EBER-negative HD, 8 yielded PCR products indicating presence of het EBV DNA. Two of these contained defective EBV in the apparent absence of the prototype virus. Of the 42 tumors analyzed for defective EBV by both PCR techniques, there was concordance of results in 38 (90%). Detection of defective EBV genomes with the potential to disrupt viral gene regulation suggests one mechanism for pathogenic diversity that may also account for loss of prototypic EBV from individual tumor cells.

Adult↗

PubMed1991

Assembly and analysis of a functional vaccinia virus "amplicon" containing the C-repeat region from the M protein of Streptococcus pyogenes.

Previous studies have shown that when inoculated intranasally into mice, vaccinia virus (VV) recombinants expressing the carboxyl half of the Streptococcus pyogenes M protein [which contains the C-repeat region (CRR)] could elicit a protective immune response against subsequent challenge by both homologous and heterologous serotypes of pathogenic group A streptococci. In the present study, an insertion plasmid was constructed that contained three tandem in-frame repeats of a 310-base-pair DNA sequence encoding the CRR from streptococcal M6 protein under control of a constitutive viral promoter. The plasmid was used to introduce the bacterial sequences into the VV genome by homologous recombination. Surprisingly, the recombinant VV:CRR3X virus that was isolated appeared to represent not an individual recombinant virus but a complex mixture of variants that contained from 1 to greater than 20 tandem copies of the CRR region at the insertion site. This genomic complexity was mirrored at the transcriptional level in that a nested set of coterminal transcripts was detected in VV:CRR3X-infected cells, which increased in size from 1400 to 6600 bases by increments of approximately 300 bases. All transcripts containing two or more CRR inserts appeared functional, as Western (immuno) blot analyses of VV:CRR3X-infected cell extracts revealed a family of CRR-related proteins with apparent molecular masses that increased from 30 kDa upward in increments of 10 kDa. All data are consistent with the hypothesis that variation in the VV:CRR3X recombinants is from random crossover events that occur within the CRR region during viral DNA replication. These results suggest that the genomic diversity generated by the "recombinogenic" properties of vaccinia recombinants containing tandem foreign inserts could be used to facilitate induction of a broadly protective immune response against antigenically diverse pathogenic agents.

Amino Acid Sequence↗

PubMed1994

Haplotype mapping and sequence analysis of the mouse Nramp gene predict susceptibility to infection with intracellular parasites.

The mouse chromosome 1 locus Bcg (Ity, Lsh) controls the capacity of the tissue macrophage to restrict the replication of antigenically unrelated intracellular parasites and therefore determines the natural resistance (BCG-R, dominant) or susceptibility (BCG-S, recessive) of inbred mouse strains to infection with diverse pathogens, including several Mycobacterium species, Salmonella typhimurium, and Leishmania donovani. We have used a positional cloning strategy based on genetic and physical mapping, YAC cloning, and exon trapping to isolate a candidate gene for Bcg (Nramp) that encodes a predicted macrophage-specific transport protein. We have analyzed a total of 27 inbred mouse strains of BCG-R and BCG-S phenotypes for the presence of nucleotide sequence variations within the coding portion of Nramp and have carried out haplotype typing of the corresponding chromosome 1 region in these mice, using 11 additional polymorphic markers mapping in the immediate vicinity of Nramp. cDNA cloning and nucleotide sequencing identified 5 nucleotide sequence variations within Nramp in the inbred strains; while 4 of these represented silent sequence polymorphisms, one G to A substitution at nucleotide position 783 resulted in the non-conservative replacement of Gly105 to Asp105 within the second predicted transmembrane domain (TM2) of the Nramp protein. An absolute association of this allelic variation and Bcg phenotype was observed in the 20 BCG-R strains (Gly105) and 7 BCG-S strains (Asp105) tested. Moreover, sequence analysis of the corresponding region of the Nramp gene from distantly related species indicated strong amino acid sequence conservation of TM2, including an invariant glycine at position 105. Haplotype mapping using sequence polymorphism identified within Nramp and additional RFLPs and SSLPs from the region revealed that although the 20 BCG-R strains analyzed showed diverse allelic combinations for these markers, the 7 BCG-S strains tested share a conserved core haplotype of 2.2 Mb overlapping and including Nramp. Taken together, these results suggest that (1) Gly105 is the wildtype form of Nramp and that the nonconservative substitution to Asp105 underlies the BCG-S phenotype, and (2) Bcg8 alleles carry the same Gly105-->Asp105 mutation and are identical by descent.

Alleles↗

PubMed1997

A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen.

The development of safe and effective vaccines remains a major goal in the prevention, and perhaps treatment, of infectious diseases. Ideally, a single vaccine would confer protection against several pathogens and would induce both cellular and humoral arms of the immune response. We originally demonstrated that two virus-specific cytotoxic T-lymphocyte (CTL) epitopes, from the same virus but presented by different major histocompatibility complex alleles, when linked in tandem as minigenes in a recombinant vaccinia virus, could confer complete protection against subsequent viral challenge. In the study, we extended this approach, which we termed string of beads, expanding the immunogenic scope in two ways: first, by introduction of T helper (Th) and B-cell (antibody) epitopes alongside CTL epitopes and second, by including immunogenic sequences from a variety of infectious agents, five viruses and one bacterium. The vaccine (VV-sv) comprises CTL epitopes from Sendai virus, respiratory syncytial virus, and lymphocytic choriomeningitis virus (LCMV); Th epitopes from vesicular stomatitis virus and Mycobacterium tuberculosis; and an antibody epitope from mengovirus. The construct contains a single start codon, and the epitopes are linked directly, without intervening spacer amino acids. There was some concern that the combination of several normally immunodominant epitopes might result in a new hierarchy of dominance, in which certain epitopes predominated and others exhibited reduced immunogenicity. However we show that when analyzed in tissue culture and in vivo, all six epitopes are expressed. CTL and Th cells are induced in vivo, along with neutralizing antibody. The induced immunity is biologically relevant: after VV-sv immunization, the antimengovirus antibody confers protection against mengovirus challenge. Similarly, CTL induced by the LCMV epitope protected mice against challenge with this agent. Thus, a polyvalent, minigene-based vaccine can simultaneously induce several classes of immune response and thereby can confer protection against diverse pathogens.

Amino Acid Sequence↗

PubMed1996

Induction of NF-kB-like transcription factors in brain areas susceptible to kainate toxicity.

Administration of kainate (KA), a glutamate receptor agonist, to rats causes neuronal damage in the CA1/CA3 fields of the hippocampus and in the pyriform/ entorhinal cortex. Reactive gliosis also occurs and activated astrocytes upregulate their expression of a large number of molecules. Since NF-kB transcription factors are involved in cellular responses to diverse pathogenic stimuli and have been shown to be induced in astrocytes in vitro in response to cytokines and growth factors, we investigated their possible involvement in the changes in gene expression subsequent to KA-induced lesions. Immunoreactivity to the p65 subunit of NF-kB was markedly increased in non-neuronal cells 2 days after KA administration (8 mg/kg i.p.) in the areas of selective neuronal degeneration. This increase was not observed 3 h or 1 day after injection, but was still present 7-10 days after KA injection. By gel mobility-shift assay, a protein complex binding to the kB consensus sequence was found to be induced by 2 days after KA, which correlated with immunohistochemical findings. This NF-kB-protein complex seemed to be localized in reactive astrocytes, as indicated by the morphological similarity of NF-kB-positive cells and reactive astrocytes stained with glial fibrillary acidic protein (GFAP) antibody, and the parallelism between the time course of NF-kB induction and appearance of gliosis after KA treatment. Double immunocytochemistry experiments demonstrated the colocalization of NF-kB positive cells and reactive astrocytes. Our results suggest that activated NF-kB in astrocytes participates in delayed and long-term responses of glia to injury.

Animals↗

PubMed2000

Comparison of competing risks failure time methods and time-independent methods for assessing strain variations in vaccine protection.

In a preventive vaccine efficacy trial of a vaccine for a genotypically and phenotypically diverse pathogen, it is important to assess if and how vaccine protection against infection or disease varies with characteristics of the exposing pathogen. Gilbert, Self and Ashby developed statistical methods for this problem when the outcome data are counts of the number of vaccinated and unvaccinated trial participants infected by each pathogen strain. However, in many vaccine trials time-to-case information is available, and the extent to which this information improves investigation of differential vaccine protection is unclear. We describe how cause-specific proportional hazards models and other popular competing risks failure time techniques can be applied to this problem. This includes new results on the assumptions required for these methods to give valid inferences about strain-specific vaccine efficacy, and a comparison of theoretical and finite-sample properties between these methods and the time-independent methods. Theoretical considerations, a cholera vaccine trial example, and an extensive simulation study of a human immunodeficiency virus type 1 (HIV-1) vaccine trial show that information about failure times does not appreciably improve estimation or testing unless the pathogen has a high attack rate and the relative prevalence of pathogen strains shifts substantially during the trial follow-up period. An important implication is that practically optimal evaluation of strain-specific vaccine efficacy in HIV-1 vaccine trials will not require knowledge of infection times.

AIDS Vaccines↗

PubMed2001

Characterization of the response to myelin basic protein in a non human primate model for multiple sclerosis.

The common marmoset Callithrix jacchus (C. jacchus) is an outbred species characterized by a naturally occurring bone marrow chimerism and susceptibility to a form of experimental autoimmune encephalomyelitis (EAE) resembling multiple sclerosis (MS). T cell clones specific for the myelin antigen, myelin basic protein (MBP), can be derived from both naive and immunized marmosets and can adoptively transfer EAE to compatible chimeric siblings. Here, we demonstrate that several different antigenic determinants of MBP are recognized by these encephalitogenic T cell clones. Furthermore, PCR-based analysis of TCR Vbeta families does not show the preferential usage of any gene segment. Characterization of third complementarity determining regions (CDR3) fails to demonstrate a recurring motif characteristic of the T cell immune response to MBP in this species. Nevertheless, brief amino acid motifs are shared among marmoset clones and CDR3 sequences from MS samples. These data suggest that, due to its outbred condition, the C. jacchus marmoset mounts a diverse pathogenic response to MBP. However, the findings that certain CDR3 sequences are identically expressed in different animals, or by different T cell clones, suggest that MBP-specific T cell populations may be clonally expanded following chronic antigenic stimulation in vivo.

Amino Acid Motifs↗

PubMed2026

Molecular Bases and Genetic Design of Rice Disease Resistance for Optimized Yield and Sustainable Agriculture.

Rice diseases continue to undermine yield stability and threaten the sustainability of rice production. The central challenge is therefore not simply to maximize immune activation, but to identify genetic interventions that remain effective across diverse pathogen races and environmental conditions without imposing excessive penalties on growth or yield. Here, we synthesize the molecular basis of rice immunity from a design-oriented perspective. We first examine cell-surface pattern-recognition receptors and intracellular nucleotide-binding leucine-rich repeat receptors, and then assess the shared signaling hubs and defence outputs that connect pathogen perception to antimicrobial responses. Rather than treating these components as equivalent breeding targets, we compare their translational potential according to resistance spectrum, anticipated durability, tunability, pleiotropic risk, and the strength of field evidence. We further discuss breeding strategies based on receptor engineering, editing of susceptibility genes and cis-regulatory elements, post-translational motif engineering, pathogen-inducible and upstream open reading frame-mediated regulation, resistance-gene stacking and artificial intelligence-assisted prediction. We argue that rational resistance design in rice should move beyond constitutive immune activation toward allele-specific, quantitative, spatially restricted and infection-responsive regulation. Integrating mechanistic insights with precision genome editing, accelerated breeding and responsible deployment offers a practical route to durable, yield-compatible disease resistance while reducing dependence on chemical control.

breeding strategy↗

PubMed2006

Human ceruminous gland: ultrastructure and histochemical analysis of antimicrobial and cytoskeletal components.

The ceruminous glands in the skin of the human external auditory canal are modified apocrine glands, which, together with sebaceous glands, produce the cerumen, the ear wax. Cerumen plays an important role in the protection of the ear canal against physical damage and microbial invasion. We studied the morphology of the glandular cells by light and electronmicroscopy. Antimicrobial and cytoskeletal components of the ceruminous glands were investigated by immunohistochemical methods. Numerous antimicrobial proteins and peptides are present in the ceruminous glandular cells: beta-defensin-1, beta-defensin-2, cathelicidin, lysozyme, lactoferrin, MUC1, secretory component of IgA. These data indicate a crucial role in the innate host defense against diverse pathogens. The apocrine secretion mechanism is a special mode of secretion by which the apical part of the cell cytoplasm surrounded by a membrane is pinched off. We could show that the presence of actin filaments, CK 19 and CK 7, seems to play a role in the pinching-off mechanism. Finally, we showed the secretion of lipid vesicles from the ceruminous gland. We could extend the number of detected antimicrobial peptides and proteins in human ceruminous glandular cells that protect the surface of the external auditory meatus. In addition, we detected proteins involved in the apocrine secretion mode of the ceruminous gland.

Adolescent↗

PubMed2006

Alternating vector immunizations encoding pre-erythrocytic malaria antigens enhance memory responses in a malaria endemic area.

A heterologous prime-boost strategy has been developed to potently induce T cell responses to pre-erythrocytic malaria antigens. Efficacy in the field is likely to depend on both peak immunogenicity and the durability of responses. To improve both immunogenicity and durability of responses, 54 adult males from a malaria endemic area were immunized with different vaccination regimens, systematically varying antigenic insert and the number and sequence of component vaccinations. The component vaccinations were recombinant attenuated viruses, either fowlpox (FP) 9 or modified vaccinia virus Ankara (MVA). These were recombinant for either of two pre-erythrocytic malaria antigens (multiple epitope-thrombospondin-related adhesion protein, ME-TRAP, or circumsporozoite antigen (CS). ELISPOT assays were used to measure the effector and resting memory T cell responses. Sequence, antigen insert and number of vaccinations influenced immunogenicity, but the novel alternating vector immunizations generated the largest resting memory T cell populations. Effector responses were maintained at 84% of the peak response after 270 days. This durability of response is unprecedented. Classical prime-boost vaccination responses were at 5% of the peak after 270 days. Vaccines administered by heterologous prime-boost regimes are being developed for diverse pathogens and cancer. These data suggest these vaccines should also be administered by alternating vector regimens in clinical development.

Adolescent↗