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At least 865 records · Page 48Linked to original sources
PubMed2025

Diversification of an emerging bacterial plant pathogen; insights into the global spread of Xanthomonas euvesicatoria pv. perforans.

Emerging and re-emerging plant diseases continue to present multifarious threats to global food security. Considerable recent efforts are therefore being channeled towards understanding the nature of pathogen emergence, their spread and evolution. Xanthomonas euvesicatoria pv. perforans (Xep), one of the causal agents of bacterial spot of tomato, rapidly emerged and displaced other bacterial spot xanthomonads in many tomato production regions around the world. In less than three decades, it has become a dominant xanthomonad pathogen in tomato production systems across the world and presents a compelling example for understanding diversification of recently emerged bacterial plant pathogens. Although Xep has been continuously monitored in Florida since its discovery, the global population structure and evolution at the genome-scale is yet to be fully explored. The objectives of this work were to determine genetic diversity globally to ascertain if different tomato production regions contain genetically distinct Xep populations, to examine genetic relatedness of strains collected in tomato seed production areas in East Asia and other production regions, and to evaluate variation in type III secretion effectors, which are critical pathogenicity and virulence factors, in relationship to population structure. We used genome data from 270 strains from 13 countries for phylogenetic analysis and characterization of type III effector gene diversity among strains. Our results showed notable genetic diversity in the pathogen. We found genetically similar strains in distant tomato production regions, including seed production regions, and diversification over the past 100 years, which is consistent with intercontinental dissemination of the pathogen in hybrid tomato production chains. Evolution of the Xep pangenome, including the acquisition and loss of type III secreted effectors, is apparent within and among phylogenetic lineages. The apparent long-distance movement of the pathogen, together with variants that may not yet be widely distributed, poses risks of emergence of new variants in tomato production.

Xanthomonas↗
PubMed2006

[Genetic variants of Mycobacterium tuberculosis isolated from patients of the Xth Region of Chile].

The emergence of new virulent and drug resistant strains of Mycobacterium tuberculosis has forced researchers to focus on the worldwide geographical distribution of the genetics variants of this pathogen. Mycobacterium bovis, a close related pathogen, contributes with human tuberculosis and therefore, it is particularly important in countries with significant bovine tuberculosis prevalence. Spoligotyping is currently one of the most widely used strategies for genotyping members of the M. tuberculosis complex. In this work, of a total of 41 isolates, 25 were from different patients from the Xth Region from Chile. These isolates formed 15 clusters of spoligotypes. Twenty four percent of the spoligotypes corresponded to the worldwide distributed spoligotype 53 (SpolDB4). A significant number of spoligotypes were identical to profiles found in Brazil followed by Argentina and Spain. Although the patients where from rural areas, no cases of zoonosis were observed. To establish the geographical distribution, persistence and routes of dissemination of the pathogen, a greater number of epidemiologically relevant isolates are being analyzed using the MIRUs-VNTRs.

Bacterial Typing Techniques↗
PubMed1981

Recovery of a Lassa-related arenavirus in Zimbabwe.

Immunofluorescent antibodies to "Mozambique" virus, a close relative of Lassa virus, were found in 11 of 55 Mastomys natalensis and 1 of 13 Aethomys chrysophilus rodents captured near Que Que and Chiredzi, Zimbabwe. Six strains of Mozambique virus, identified by use of specific monoclonal antibodies to the agent, were recovered from visceral tissues of M. natalensis rodents. All Mastomys having virus or antibodies to this agent were of the chromosomal form 2N = 32 (M. natalensis). These data extend the area of geographic occurrence of this virus, which was initially recognized in Mozambique and which may represent a naturally attenuated antigenic variant of human pathogenic West African Lassa virus.

Animals↗
PubMed2005

[Gait and stability disorders of the elderly. Clinical analysis of a series of 259 patients older than 70 years].

INTRODUCTION: Gait and stability disorders of the elderly are frequent and a cause of disability, but studies on their clinical features and etiology are scarce, including the relationship between both disorders. OBJECTIVES: To evaluate an extensive series of patients with gait and stability disorders, its clinical variants and posible pathogenic significance. PATIENTS AND METHODS: 259 patients older than 70 years consulting for chronic gait and stability symptoms in an outpatients neurologic clinic were retrospectively reviewed. Several clinical and evolution data are analyzed. RESULTS: Mean age was 78.8 years and 61.8% were women. 52 % were hypertensive. 161 cases had disequilibrium, 91 a cautious gait and seven other types of gait abnormality. 11 % had associated dementia. 27 % showed subcortical white matter abnormalities on computed tomography scan. In 28 cases a specific cause could be established. In follow-up 33.5 % worsened. Significant differences between cases of disequilibrium and cautious gait were increased age, functional disability and turn abnormality in the latter. CONCLUSIONS: Disequilibrium and cautious gait of the elderly share some clinical features, have few specific causes and vary from mild cases to a disabling < >.

Accidental Falls↗
PubMed2006

Fine mapping of the keratoconus with cataract locus on chromosome 15q and candidate gene analysis.

PURPOSE: To report the fine mapping of the keratoconus with cataract locus on chromosome 15q and the mutational analysis of positional candidate genes. METHODS: Genotyping of two novel microsatellite markers and a single nucleotide polymorphism (SNP) in the critical region of linkage for keratoconus with cataract on 15q was performed. Positional candidate genes (MORF4L1, KIAA1055, ETFA, AWP1, REC14, KIAA1199, RCN2, FAH, IDH3A, MTHFS, ADAMTS7, MAN2C1, PTPN9, KIAA1024, ARNT2, BCL2A1, ISL2, C15ORF22 (P24B), DNAJA4, FLJ14594, CIB2 (KIP2), C15ORF5, and PSMA4) prioritized on the basis of ocular expression and probable function were screened by PCR-based DNA sequencing methods. RESULTS: We report the refinement of the linkage region for keratoconus with cataract to an interval of approximately 5.5 Mb flanked by the MAN2C1 gene and the D15S211 marker on chromosome 15q. Mutational analysis of positional candidate genes detected many sequence variations and single nucleotide polymorphisms. None of the sequence variants were considered pathogenic as they were also found in unaffected family members and normal control DNA samples. CONCLUSIONS: Fine mapping of the keratoconus with cataract locus on 15q has reduced the linked region to 5.5 Mb, thereby excluding 28 candidate genes. A further 23 candidate genes were excluded by direct sequencing methods, although a pathogenic genomic rearrangement or exonic deletion would not have been detected.

Case-Control Studies↗
PubMedDate not supplied

[Development of immunity to the poliomyelitis virus in infants with various methods of administering a live poliomyelitis vaccine].

The data have been obtained which indicate that the effectiveness of vaccination with live trivalent poliomyelitis vaccine may be increased and 90--100% of the vaccinated infants under 1 year of age may develop marked resistance of the alimentary tract and high antibody titers in the blood serum to the threee types of poliomyelitis virus in the course of 3 vaccinations. Some regularities of the formation of immunity to individual poliomyelitis virus types in the course of 4 vaccinations with trivalent vaccine were revealed and specified. The results indicate that the contact of vaccine virus with the oropharyngeal tissues during immunization has a favourable effect on the development of immunity. Vaccination of infants under 1 at 6-week intervals between vaccine feedings creates solid immunity in 90--100% vaccines. Administration of the next vaccine dose 6 weeks after the previous one stops multiplication of the dominating type of vaccine virus and prevents its long-term passage in the intestinal tract decreasing the probability of emergence of vaccine virus variants with increased pathogenicity.

Antibodies, Viral↗
PubMed1986

Stability of rubella virus after long-term persistence in human cell line.

Primary infection of HEp-2 cells with rubella virus resulted in non-cytophatic long-term persistent infection. During four years of persistence the virus was produced in sufficient quantities (up to 6 logs PFU/ml) and did not differ from the parental variant in its pathogenicity for BHK-21 or RK-13 cells, or hemagglutinating activity, but formed smaller plaques. Persistent virus preserved the original antigenicity as judged from reciprocal hemagglutination-inhibition or plaque reduction-neutralization tests with polyclonal antisera. Both original and persistent rubella viruses were thermoresistant (T 56 degrees C) and slightly temperature-sensitive. Clonal analysis revealed presence of ts-mutants among both original and persistent virus clones with different degrees of plating efficiency at 40 degrees/34 degrees C. RNA fingerprinting showed only minor changes in persistent rubella virus.

Antigens, Viral↗
PubMed1984

[Sensitivity of different morphological variants of Leptospira to the leptospirocidal activity of normal animal sera].

The leptospirocidal activity of normal animal sera with respect to 23 Leptospira strains was experimentally studied in vitro. 91.3% of the strains under study proved to be sensitive to the lytic action of cattle serum and 86.9%, to sheep serum. The uncinate variants of the pathogenic strains showed resistance to the action of the above sera, and their nonuncinate analogs were subject to agglutination with subsequent lysis, similarly to saprophytes.

Animals↗
PubMed1994

[Differential-diagnostic value of detecting L-forms of Mycobacterium tuberculosis].

A clinical and bacteriological study was made of 144 patients with new-onset pulmonary tuberculosis who had been treated within the first 3-4 weeks in the out- and in-patient settings for non-specific lung disease. Detailed studies found changed variants of the pathogen as L-forms in 28 (19.4%) patients, bacterial forms being undetectable. The paper shows how difficult to diagnose tuberculosis.

Adult↗
PubMed1993

[New vaccines in the age of genetic engineering].

The era of genetic engineering is merely 20 years of age, yet has already borne completely new perspectives for vaccine development. Important insights are gained by elucidating the genetic information of a disease-causing microorganism and its pathogenic and attenuated variants. Site-directed mutagenesis can then be employed to specifically alter the genetic information in a variety of ways. Upon transfer of the corresponding gene to pro- or eucaryotic cells, large quantities of microbial components can be produced. A new generation of such subunit vaccines is already undergoing clinical testing. Recently, hybrid vaccines have been constructed, which utilize highly successful traditional live vaccines such as polio- and vaccinia-virus or the Tbc-bacterium as carriers for components of other microorganisms. We should bear in mind that the same new technologies can be abused for the construction of potentially dangerous biological weapons. The scientific community bears the responsibility to prevent such abuse and to lobby for an easy access to the new vaccines by the world's poorest inhabitants.

Bacterial Vaccines↗
PubMed1976

Interfering activity of virulent and attenuated influenza virus strains.

The interfering activity of influenza virus variants A/Hong Kong/1/68 (H3N202), A/Victoria/35/72(H3N2-3), B/14/55 and B/USSR/69 differing in the level of their reactogenicity for adults and children was studied. An inverse relationship was established between reactogenicity of the strains and their interfering activity in the resistant chick embryo cell (CEC) cultures. Virulent strains did not interfere with vesicular stomatitis virus. Vaccine strains used for commercial live influenza vaccine safe for adults but reactogenic in children were intermediate and showed moderate interfering activity. The highest capacity for interference was demonstrated in cold-adapted thermosensitive variants non-pathogenic for both adults and children. The interfering activity of the attenuated strains increased progressively with increasing inocula.

Adult↗
PubMed2025

Identification of IDH3G, encoding the gamma subunit of mitochondrial isocitrate dehydrogenase, as a novel candidate gene for X-linked retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerative disorders characterized by the loss of rod and cone photoreceptors, leading to visual impairment and blindness. To date, to our knowledge, X-linked RP has been associated with variants in 3 genes (RPGR, RP2, and OFD1), whereas genetic defects at 3 loci (RP6, RP24, and RP34) are yet unidentified. The aim of this study was to identify a novel candidate gene underlying X-linked RP. METHODS: Participants were identified from cohorts of genetically unsolved male individuals affected by RP, who underwent genome sequencing, exome sequencing, or candidate gene screening via direct Sanger sequencing at 3 referral centers. Specifically, 2 probands were identified at the National Reference Centre for Rare Retinal Diseases (Paris, France), 2 at the Massachusetts Eye and Ear Hospital (Boston, MA), and 1 at the National Reference Centre for Inherited Sensory Diseases (Montpellier, France). The pathogenicity of the identified variants was assessed using bioinformatic predictions, protein expression analyses, and mitochondrial function assays. RESULTS: We identified 4 rare single-nucleotide variants in IDH3G (HGNC:5386), located at the RP34 locus on the X chromosome, and a complete gene deletion, in 5 unrelated male individuals affected with nonsyndromic RP. The variants segregated with the phenotype in all available family members. In all cases, the disease severity was intermediate. None had high myopia. IDH3G encodes the &#x3b3; subunit of mitochondrial isocitrate dehydrogenase (IDH3), an enzyme involved in the citric acid cycle, which is expressed in the inner segments of photoreceptors. Variants in IDH3A and IDH3B, encoding the other subunits of IDH3, have already been associated with nonsyndromic autosomal recessive RP. Bioinformatic predictions and functional assays support a pathogenic role for the variants identified in this study, possibly through partial loss of enzymatic activity and mitochondrial function. CONCLUSION: Our findings suggest that variants in IDH3G are a novel cause of X-linked RP.

Humans↗
PubMed2003

Early onset familial Alzheimer's disease: Mutation frequency in 31 families.

BACKGROUND: Three causative genes have been identified for autosomal dominant AD. OBJECTIVE: To determine the proportion of patients with early onset AD with a positive family history accounted for by mutations in these genes. METHODS: A mutational analysis of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes was performed in 31 probands with probable or definite AD from UK families with an age at onset (AAO) <61 years. RESULTS: The mean AAO was 46.9 years (median 45 years; range 33 to 60 years). The majority of patients (23 of 31; 74%) fulfilled recognized criteria for autosomal dominant inheritance. In 17 (55%) probands the authors identified eight novel PSEN1 sequence variants and eight recognized pathogenic mutations. In 4 (13%) probands the authors identified one novel APP sequence variant (H677R) and two recognized mutations. Thus in this series 21 of 31 (68%) probands were associated with a sequence variant in APP or PSEN1. Nine of the 11 (82%) probands with neuropathologically confirmed AD who additionally fulfilled recognized criteria for autosomal dominant inheritance were associated with a sequence variant in APP or PSEN1. The 10 patients in whom the authors were unable to identify a mutation in APP, PSEN1, or PSEN2 were older than the probands with sequence variants (55.4 vs 44.7 years: p = 0.001). CONCLUSIONS: Sequence variants in APP and PSEN1 accounted for the majority of neuropathologically confirmed autosomal dominant early onset AD; no mutations in PSEN2 were detected. There may be a further genetic factor involved in the etiology of autosomal dominant early onset AD.

Adult↗
PubMed2024

SLC12A1 variant c.1684+1 G>A causes Bartter syndrome type 1 by promoting exon 13 skipping.

BACKGROUND: Bartter syndrome type 1, an autosomal recessive genetic disorder, is caused by pathogenic loss-of-function variants in the SLC12A1 gene. It is characterized by metabolic alkalosis and prenatal-onset polyuria leading to polyhydramnios. METHODS: We identified pathogenic gene in a 12-day-old newborn boy with Bartter syndrome type 1 using whole-exome sequencing. Sanger sequencing validated the identified variants. A minigene assay was performed to investigate the effect of a novel splice site variant on pre-mRNA splicing. RESULTS: We found a compound heterozygous variants in the SLC12A1 gene, consisting of a known pathogenic missense mutation (NM_000338: c.769 G>A; p.Gly257Ser) and a novel splice site variant (c.1684+1 G>A). In silico predictions and an in vitro minigene splicing assay demonstrated that the splicing variant c.1684+1 G>A abolished a consensus splice donor site of SLC12A1 intron 13, resulting in complete exon 13 skipping, translational frameshift, and premature termination codon, ultimately leading to loss of SLC12A1 function. CONCLUSION: Using a cell-based in vitro assay, we revealed the aberrant effect of the pathogenic splicing variant SLC12A1 c.1684+1 G>A on pre-mRNA splicing. Our findings expand the gene mutation spectrum of Bartter syndrome type 1, providing a basis for genetic diagnosis and the development of genetic medicines.

Humans↗
PubMed1980

Novel expression-linked copies of the genes for variant surface antigens in trypanosomes.

Pathogenic African trypanosomes evade the immune system of their mammalian hosts by the sequential expression of alternative cell-surface glycoproteins (reviewed in refs 1,2). Variant surface glycoproteins (VSGs) purified from cloned variants of Trypanosoma brucei have similar molecular weights (about 60,000), but differ in amino acid composition, N-terminal amino acid sequence and C-terminal structure. We have cloned DNA complementary to the messenger RNA's for four immunologically distinct VSGs and hybridised these complementary DNAs (cDNAs) with restriction digests of T. brucei nuclear DNA, fractionated by gel electrophoresis and transferred to nitrocellulose strips. Each cDNA recognises a unique set of fragments and this basic set is present unaltered in the nuclear DNAs from the four variants. In addition, each probe recognises an extra fragment only in nuclear DNA isolated from cells expressing the VSG corresponding to the cDNA probe. We infer that activation of a VSG gene involves the production of an expression-linked copy of that gene.

Animals↗
PubMed2026

Toward a unified approach: Considerations for bioinformatic and sequencing activities & data in wastewater surveillance of biologic public health threats.

Genomic technologies such as PCR and next-generation sequencing (NGS) have greatly advanced public health surveillance, especially during COVID-19, by enabling detailed tracking of pathogen spread, origins, and variants. While PCR is vital for targeted detection, falling NGS costs have made large-scale, high-throughput sequencing more feasible, supporting broader pathogen monitoring-including the detection of vaccine escape variants and new strains. Applying NGS to wastewater offers valuable population-level insights but faces challenges such as variable sample complexity, the need for skilled staff, suitable platforms, and robust IT infrastructure. Although there are currently a lot of efforts towards defining guidelines for sampling, analysis, and integrating wastewater data into public health policy, such as the recently published International Cookbook for Wastewater Practitioners, they often lack universal applicability, emphasizing the analytical approaches in favour of the NGS-based approaches. However, standardising protocols for sampling, sequencing, and analysis is crucial to ensure reliable, comparable data across surveillance systems worldwide. Pilot studies and continuous refinement are recommended to overcome implementation hurdles and fully realise the benefits of NGS in wastewater surveillance. This work attempts to outline these challenges and opportunities across the entire wastewater surveillance workflow, from data generation to reporting, and provide some concrete suggestions and considerations across the spectrum of activities. We further highlight that the infrastructure, funding and government-policy context in which surveillance operates acts as an enabling condition for these activities, and that technical standardisation alone is unlikely to deliver durable, comparable surveillance in its absence.

considerations↗
PubMed1994

Phase variation in streptococci of serological group B. Characteristic properties of isolates from human and bovine infection.

Encapsulation is thought to be a critical virulence factor in streptococci of serological group B. In the present study two encapsulated low-density variants could be separated from their unencapsulated original strains by Percoll gradient centrifugation. The original strains had been isolated from human endocarditis and bovine mastitis. Type antigen preparations of the encapsulated human and bovine group B streptococcus reacted with type III- and type IV-specific antiserum, respectively. No comparable reactions could be observed with their unencapsulated parent strains. In contrast to the original strains, the encapsulated variants grew with uniform turbidity in fluid medium and formed diffuse colonies in soft agar. The original strains grew as granular sediment and formed compact colonies in soft agar. In addition, the original strains appeared to have a more hydrophobic surface and showed significantly greater adherence to epithelial cells. In contrast to the nonencapsulated parent strains, the encapsulated variants were less phagocytosed by polymorphonuclear leukocytes. These findings may help our understanding of the pathogenic importance of phase variants in infections with this bacterial organism.

Animals↗