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PubMed2003

Travel epidemiology--a global perspective.

In order to have a rational approach to necessary preventive measures it is essential to know the health risks. The 80 million travellers each year with destinations in Africa, Asia, Latin America, Pacific Islands and remote areas in Eastern Europe are exposed to a broad range of pathogens that are rarely encountered at home. The risk depends on the degree of endemicity in the area visited, the duration of stay, the individual behaviour and the preventive measures taken. Travellers' diarrhoea (TD) is the most frequent ailment of visitors to countries with poor hygiene. The incidence rate is 25-90% in the first 2 weeks abroad. The risk of TD is far less in travellers originating in a high risk country, as some immunity develops. Malaria is an important risk for travellers going to endemic areas. Without chemoprophylaxis, the monthly incidence is high in some destinations, among them frequently visited tropical Africa where 80-95% of the infections are due to Plasmodium falciparum. The incidence rates are lower in most endemic areas of Asia and Latin America where Plasmodium vivax predominates. The risk is nil in all capital cities of South America and SE Asia, as well as in many frequently visited tourist destinations. The diseases preventable by immunization will be discussed in a separate paper (Vaccination priorities; page 175). Sexually transmitted diseases occur frequently, as some travellers (5% of Europeans) engage in casual sex, approximately half of them without being protected by a condom. The prevalence for HIV-infection, syphilis, gonorrhoea, etc. often exceeds 50% in prostitutes. In some European countries, a major proportion of heterosexuals with newly acquired HIV-infection have acquired it while abroad.

Accidents↗

PubMed1992

Apoptosis in the development of the immune system: growth factors, clonal selection and bcl-2.

The mammalian immune system is essential for surviving challenge infections with a great range of potential pathogens. The protective effect produced is dependent on many different types of cells which require flexible and independent production and regulation. In particular, many important responses are carried out by lymphocytes, which recognise foreign antigen through exquisitely specific receptors: i.e. surface immunoglobulin (sIg) on B lymphocytes and the T cell receptor (TCR) on T lymphocytes. Each lymphocyte displays receptors with a single specificity, allowing cells with particular specificities to be regulated independently. Since millions of different Igs and TCRs are expressed, the precise selection and regulation of each T and B cell population to produce a useful self-tolerant repertoire is a very complex process. Control of cell populations can, in theory, be exercised at a number of levels, including modulation of active cell death by apoptosis. Recent research has demonstrated that regulation of apoptosis is indeed a crucial element in the control of the immune system in general, and in the development of the TCR and Ig repertoires in particular. The molecular analysis of apoptosis now takes a high priority and the proto-oncogene bcl-2 appears to be responsible for specific suppression of apoptosis in several important situations. It is also clear that malfunctions affecting apoptosis, and in particular bcl-2, can result in significant progression towards malignancy.

Animals↗

PubMedDate not supplied

The impact of respiratory viral infections in patients with cystic fibrosis.

Respiratory viruses have been implicated in pulmonary exacerbations of CF and in the long-term course of pulmonary dysfunction in these patients. However, the data are by no means complete and there is the clear need for more intensive evaluations of the role of viral pathogens in this population. Further controlled prospective studies assessing the impact of viral infections in large cohorts of patients with CF are still necessary. Placebo-controlled, antiviral treatment protocols also should be initiated. In clinical practice at the present time, patients with CF should be assessed for respiratory viral infections, at least at the time of hospitalizations for pulmonary deterioration. This assessment should include obtaining specimens from the respiratory tract for viral cultures and rapid respiratory viral antigen detection. Identifying a respiratory viral infection may alter clinical care. The patient can be isolated appropriately, and it may be possible to reduce the intensive use of expensive and potentially toxic parenteral antibiotics. The role of antiviral therapy in these patients must await further evaluations. The mechanisms of the short- and long-term effects of respiratory viruses in patients with CF have not been defined. However, pathophysiologic studies conducted in normal children and adults allow the development of several plausible hypotheses. The definition of mechanisms of injury in this population must be a priority, since it may influence clinical practice. If airway obstruction is the principal mechanism of viral-induced injury, therapeutic approaches designed to relieve the obstruction would be most appropriate. For example, if the obstruction resulted from induced or aggravated reactive airway disease, the current common practice of prescribing chronic bronchodilator therapy would be appropriate. This therapy might be especially suited to those experiencing frequent viral infections. In addition, the administration of bronchodilators to patients during acute exacerbations of pulmonary disease caused by viruses might be of clinical benefit. If, on the other hand, the principal mechanism of viral-induced injury is found to be through synergistic interaction with bacteria, the current practice of aggressive antimicrobial therapy would remain appropriate.

Cystic Fibrosis↗

PubMed2026

SARS-CoV-2 intra-host variation shows evidence of transmission and convergent evolution in a university surveillance cohort.

Monitoring and understanding the transmission and evolution of SARS-CoV-2 remains a significant public health priority. Within-host genetic variation provides insight into viral evolution during infection and may help infer transmission events. In this study, we analysed intra-host variation in SARS-CoV-2 genome sequences from Boston University's testing mandate. Focusing on intra-host single nucleotide variants (iSNVs), we inferred transmission events and assessed the selective forces shaping within-host viral evolution. To minimize false-positive iSNVs resulting from systematic biases, we implemented stringent data filtering and developed a heuristic to exclude contamination-derived artefacts arising from batched sequencing. We find that intra-host variation is limited and infrequently transmitted during acute infections, suggesting that shared iSNVs serve as highly specific but insensitive markers of transmission. We also observed incomplete purifying selection shaping within-host diversity, with the loci most affected changing among variants of concern. Finally, we identified a highly recurrent iSNV (G11083T) which may represent a site of positive selection. Our results highlight that within-host variation provides insight into within-host pathogen evolution, in spite of its limited use in genomic epidemiology.

SARS-CoV-2↗

PubMed1999

The clay feet of the malaria giant and its African roots: hypotheses and inferences about origin, spread and control of Plasmodium falciparum.

Grassi's allegory of the fragile feet of clay of the malaria giant applies particularly to Plasmodium falciparum marginal populations in temperate climates such as those that spread within the last three thousand years in the Mediterranean area through their close association with non diapausing vectors of the Anopheles maculipennis complex. The winter survival of the vector and the successful completion of the sporogonic cycle depended on the availability of the house environment to the mosquito. The fragility of the parasite's cycle became especially evident with the crucial impact of indoor-sprayed residual insecticides resulting in very rapid malaria eradication. The malaria giant showed to possess much more solid feet in the Tropics where P. falciparum eventually reached an exceptionally stable endemicity in sub-Saharan Africa due to a vectorial system which produces inoculation rates far higher than the minimum necessary to saturate human populations. This very high transmissibility resulting from recent human-dependent speciation processes in Afrotropical Anopheles mosquitoes (namely the emergence in the Neolithic period of specifically anthropophilic taxa in the An. funestus and An. gambiae complexes) had probably a key influence on the origin of the modern P. falciparum from an ancestral, less pathogenic, taxon. It is hypothesised that under the prevalence of multiple inoculation during epidemic flashes, a fast growing, aggressive strain responsible for acute, short-lived infections was selected. This quickly replaced the ancestral taxon and spread all over the world taking advantage of previous Anopheles radiation and of the demographic expansion following the agricultural revolution. Dealing with the African 'roots' of the malaria giant means to face both the exceptional stability of the parasite cycle and the risk of disrupting the human natural response with unsustainable interventions. Most efforts should be concentrated in the support and improvement of the available anti-disease strategies whereas the development of effective anti-infection strategies should be mainly pursued through reasonably diversified research programmes and well monitored pilot interventions within a long-term perspective. The aim is to discover and test new anti-malarial tools which either alone or, more probably, integrated with the available measures, could allow the interruption of transmission. In most Afrotropical hyper- and holoendemic zones, once given full priority to strengthening disease control, P. falciparum eradication appears the only realistic anti-infection objective, unless it is demonstrated that progress can be achieved in these epidemiological zones through sustainable and cost-effective intermediate steps based on the reduction of infection prevalence.

Africa↗

PubMed1998

A retrospective review of the frequency of infections and patterns of antibiotic utilization on a palliative care unit.

Various disease-related and therapy-induced factors make cancer patients susceptible to infections. The epidemiology and management of infections in neutropenic cancer patients and patients with primary hematological malignancies has been widely reported, but very few studies have characterized infections and their management in palliative care patients. We conducted a retrospective review of 100 consecutive admissions to an acute palliative care unit with the objective of assessing overall and site-specific frequencies of infections, the pathogens involved and their antibiotics sensitivities, and the pattern of antibiotic utilization. The mean age was 64 +/- 11.5 years, the mean length of stay was 29.8 +/- 28.2 days, and 70% of patients died on the unit. Only one case of neutropenia was identified. Fifty-five of the 100 patients were diagnosed with a total of 74 separate infections. The most frequent sites of infections were the urinary tract (39.2%), the respiratory tract (36.5%), skin and subcutaneous tissues (12.2%), and blood (5.4%). Fifty-four culture-positive infections were identified. Overall, the most common organisms were Escherichia coli (22.9%), Staphylococcus aureus (20%), and Enterococcus (11.4%). Fifty-three of the 74 (71.6%) infections were treated with antibiotics. The decision-making process regarding treatment versus nontreatment of an infection can be complex in terminally ill patients and needs to be individualized. Symptom control is the primary objective in the majority of cases. The appropriate management of infections, with specific attention to measures that would improve patients' quality of life, should be a research priority in patients with advanced cancer.

Aged↗

PubMed2004

Management and control of nematode parasites of small ruminants in the face of total anthelmintic failure.

Total failure of modern broad spectrum anthelmintics to control nematode parasites of sheep and goats is a reality, of rapidly increasing dimension, on many farms in the tropical / subtropical regions of the world. This is primarily associated with the highly pathogenic, blood sucking parasite, Haemonchus contortus, and where it now cannot be controlled by chemotherapy, annual mortalities exceeding 20% of the flock can be expected. Thus sheep and goat enterprises become totally unsustainable, unless major changes in management are effected. These must include a change away from reliance on suppressive anthelmintic treatment and to include several non-chemotherapeutic management options. In situations where livestock numbers need to be preserved and there is no opportunity to increase the grazing area available, then zero grazing with cut-and-carry herbage from uncontaminated pasturelands is the only option. In other circumstances stocking rates need to be substantially reduced, so that short-term rotational grazing can be effectively practiced. This strategy is improved if it is combined with the biological control of the free-living stages of the parasites, using the microfungus Duddingtonia flagrans. Monitoring the parasitological status of the animals by faecal sampling sentinel sub-flocks for nematode faecal egg counts, or the use of the FAMACHA procedure, are also valuable tools. Improving overall nutrition of the flock is an important adjunct to control. As a long-term priority, attempts to change the genotype of the flocks to those breeds that have been shown to possess natural resistance to H. contortus are worthwhile.

Journal Article↗

PubMedDate not supplied

[Sanitary and epidemiological well-being: topical problems].

The interaction of the interested services and authorities in implementing a package of goal-oriented organizational, comprehensive preventive and antiepidemic measures has given stability of the sanitary-and-epidemiological situation in the Russian Federation in some recent years. To accomplish the tasks, particularly those in developing a package of measures to reduce the prevalence of infectious diseases, the "Health" national program has been drawn up for 2006-2007 this year. One of the priorities of the program is to enhance the prophylactic orientation of the public health care system. Within the framework of this direction, it is planned to provide a further steady decline in the incidence of infections controlled by specific preventive means, primarily, in that of hepatitis B and rubella, to eliminate the congenital rubella syndrome, and to maintain the status of the Russian Federation as a poliomyelitis-free area. The subjects of the Russian Federation should redistribute allocations, by taking into account the funds envisaged in the Health program for purchase of vaccines, and direct them for implementation of other measures, such as personnel training, refrigerating equipment purchase, information-propagandistic work among the population, etc. In 2005, the poor situation established in the world due to the spread of avian influenza and there was a possible threat of influenza pandemic. Investigations ascertained the identity of influenza A virus (H5N1) isolated in the Russian Federation with the South-Eastern Asia-isolated viruses that caused mass epizooties of birds and severe diseases in persons contacting infected birds. It was assumed that 2006 spring migration might lead to the spread of pathogenic influenza H5N1 viruses throughout European Russia. This was due to the fact that the birds migrating to European Russia and a portion of birds migrating from Siberia have common winter nesting areas. To prevent mass influenza virus-infected birds' death and human infection in the epizootic localities, the federal surveillance service for protection of users' rights and human well-being jointly with the federal veterinary and phytosanitary surveillance service, and public health care administrative bodies has organized and implemented a package of measures: active headquarters have been set up in the epizooty-afflicted subjects to coordinate activities in localizing the spread of epizooty of birds; emergency commissions and antiepizootic commissions have been held; regulatory documents on the Russian Federation's subjects have been published; daily collection, analysis, systematization, and exchange of information between interested services, et. are under way.

Animals↗

PubMed2003

Effect of chlorination of drinking-water on water quality and childhood diarrhoea in a village in Pakistan.

To evaluate the importance of public-domain transmission of pathogens in drinking-water, an intervention study was carried out by chlorinating the public water-supply system in a village in Pakistan. The water quality improved and reached a geometric mean of 3 Escherichia coli per 100 mL at the last standpipe of the water-supply system. Drinking-water source used and the occurrence of diarrhoea were monitored on a weekly basis over a six-month period among 144 children aged less than five years in the village. In this group, the children using chlorinated water from the water-supply scheme had a higher risk of diarrhoea than children using groundwater sources, controlled for confounding by season and availability of a toilet and a water-storage facility. The incidence of diarrhoea in the village (7.3 episodes per 10(3) person-days) was not statistically different from that in a neighbouring village where most children used water from a non-chlorinated water-supply system with very poor water quality. In this study area, under non-epidemic conditions, the reduction of faecal bacteria in the public drinking-water supply by chlorination does not seem to be a priority intervention to reduce childhood diarrhoea. However, the study was of limited size and cannot provide conclusive evidence.

Calcium Compounds↗

PubMed2003

Breast cancer genetics in African Americans.

BACKGROUND: An overview of the state of genetic testing for BRCA1 and BRCA2 genes was presented at the Summit Meeting on Breast Cancer Among African American women. METHODS: An exhaustive literature search was performed using PubMed and abstracts published from meetings of the American Association for Cancer Research, the American Society of Human Genetics, and the American Society of Clinical Oncology. The Breast Cancer Information Core was also searched for information regarding sequence variants in which the ethnicity of the individual tested was known. RESULTS: Of the 26 distinct BRCA1 pathogenic mutations (protein-truncating, disease-associated missense, and splice variants) detected in Africans or African Americans, 15 (58%) have not been previously reported. In addition, 18 deleterious BRCA2 mutations have been identified and 10 (56%) of these are unique to the group. Only two pathogenic BRCA1 mutations (943ins10 and M1775R) have been detected in three or more unrelated families. However, seven additional BRCA1 or BRCA2 deleterious mutations have been reported in at least two unrelated families. Three of these recurrent BRCA1 mutations (943ins10, 1832del5, and 5296del4) have been characterized by haplotype studies and each likely arose from a common ancestor, including one ancestor that could be traced to the Ivory Coast in West Africa. Although only a few African-American families have been tested for BRCA1 and BRCA2 mutations, the probability of finding a mutation is invariably dependent on the age of onset and the number of breast and/or ovarian cancer cases in the family. The psychosocial implications of genetic testing for African Americans have not been well studied, so that high-risk African Americans may underestimate their risks of breast and ovarian cancer. CONCLUSIONS: Deleterious BRCA1 and BRCA2 mutations have been identified in African-American and African families. A number of unique mutations have been described, but recurrent mutations are widely dispersed and are not readily identifiable in the few families that have been tested. Access to genetic counseling and testing in a culturally sensitive research setting must remain a high priority before genetic testing can be disseminated in the community.

Black People↗

PubMed2000

A burn prevention program as a long-term investment: trends in burn injuries among Jews and Bedouin children in Israel.

In order to broaden our long-term intervention efforts in elementary schools in Israel (underway since 1988) and to set priorities for further population-specific actions, we compared the pattern of burn injuries among two age groups (0-4; 5-14) of two ethnic groups of Jews and Bedouins admitted to a regional hospital between 1986 and 1995 (n = 1050). The findings indicated a significant downward trend, though somewhat nonlinear, in burn admissions among the older age groups. A relatively less favorable trend was observed for the younger age groups. Consistently across years, burn rates in the younger group of Bedouin children were the highest. For the 10-year period, a significant season by ethnic group variation in burn admissions was observed, with a peak in the spring and in the wintertime for the Jews and Bedouins, respectively. A significant trend of decrease, mostly among older children, in average lengths of hospital stay, was also evident. Yet, regardless of age group and across years, Bedouin children stayed longer in the hospital than Jewish children. The overall leading causes of injury (for 1992-1995) were hot liquids (69%), fire (17%), chemicals (9.5%) and contact (2%). In our view, there is a need to address at-risk populations through environmental, community and family-oriented interventions and to venture beyond the pathogenic factors to the investigation of the salutary factors of health under diverse life conditions.

Accident Prevention↗

PubMed2000

Ovine scrapie: priorities and importance.

Ovine and caprine scrapie occupies a unique place among animal transmissive spongiform encephalopathies (TSE). It is an object of intensive biomedicinal, ecological and economical studies. Its causative agents are demonstrably associated with the development of TSE in farmed minks, goats and moufflons. Ovine strains of scrapie occurring in North America (particularly in the USA) differ from strains which occur in Europe and were present at the onset of development of TSE in three species of deer living in free nature and in captivity in the USA. The studies dealing with the development of bovine spongiform encephalopathy (BSE) of the English type have indicated justifiably that its origin is associated with one (or more) heretofore unidentified ovine strain. The development of a variant form, the Creutzfeldt-Jacob disease in humans, and transmission of the BSE agent to several families of bovidae, felidae and primates, puts stress on its zoonotic potential. All this leads to the conclusion that domesticated sheep are the decisive reservoir species of animal TSE. They have been infected to an unknown extent with the causative agent of BSE probably through contaminated meat-bone meal. The occurrence of natural ovine prion isolates with properties similar to those of the BSE agent requires that scrapie should be included in the surveillance of human and animal TSE. At present, scrapie is a noticeable disease also in other than European Communities Member States. It is on the list B of the International Epizootics Office. Many countries have initiated control of ovine scrapie. It should therefore become a topical question also in Central and Eastern European countries. Elimination or even eradication of ovine scrapie (or its causative agents) from populations of small and large domestic ruminants is the prerequisite for prevention of penetration of ovine pathogenic prions into the human feed chain. Moreover, it should be ensured that these species will be able to produce foods of a new type (immunotrition and similar) or proteins with therapeutic effects in the near future. Our study established that the PrP genotype of Valachian rams, the Slovak autochthonous breed, contains also VRQ and ARQ alleles encoding the susceptibility to scrapie. Their selection is part of the improvement of Slovak Valachian sheep towards resistance to scrapie.

Alleles↗

PubMed2005

Use of molecular markers for species identification of Korean Perkinsus sp. isolated from Manila clams Ruditapes philippinarum.

Perkinsus is the pathogen responsible for mass mortality of the Manila clam Ruditapes philippinarum. Perkinsus sp. isolated from Manila clams collected in Korean waters was assayed by polymerase chain reaction (PCR) to determine its phylogenetic affinity with other congeneric species. Regions of rRNA of Perkinsus sp. isolated from clam haemolymph were cloned and sequenced. Sequences of a non-transcribed spacer (NTS), internal transcribed spacers (ITS 1, 2) and 5.8S rRNA genes were compared to those available from other Perkinsus species. The NTS sequence of Korean Perkinsus was approximately 99.9 to 100% similar to that of P. atlanticus and 98.06 to 98.15% and 73.05 to 73.14% similar to those of P. olseni and P. marinus, respectively. The ITS 1, 5.8S rRNA and ITS 2 sequences of Korean Perkinsus showed 100% similarity to P. atlanticus and Perkinsus sp. reported from Japan. The ITS-5.8S rRNA sequences of Korean Perkinsus were 99.86 and 93.73% similar to those of P. olseni and P. marinus, respectively. The sporulation pattern and morphology of the Korean Perkinsus were very similar to those of P. atlanticus. Our data suggest that the Perkinsus sp. isolated from clams in Korean waters is P. atlanticus, which is currently synonymous with P. olseni reported from Australia. By considering that P. olseni has taxonomic priority, Korean Perkinsus sp. is accepted as P. olseni (atlanticus).

Animals↗

PubMed1994

Rotavirus vaccines and vaccination potential.

The development of a successful rotavirus vaccine is a complex problem. Our review of rotavirus vaccine development shows that many challenges remain, and priorities for future studies need to be established. For example, the evaluation of administration of a vaccine with OPV or breast milk might receive less emphasis until a vaccine is made that shows clear efficacy against all virus serotypes. Samples remaining from previous trials should be analyzed to determine epitope-specific serum and coproantibody responses to clarify why only some trials were successful. Detailed evaluation of the antigenic properties of the viruses circulating and causing illness in vaccinated children also should be performed for comparisons with the vaccine strains. In future trials, sample collection should include monitoring for asymptomatic infections and cellular immune responses should be analyzed. The diversity of rotavirus serotype distribution must be monitored before, during, and after a trial in the study population and placebo recipients must be matched carefully to vaccine recipients. Epidemiologic and molecular studies should be expanded to document, or disprove, the possibility of animal to human rotavirus transmission, because, if this occurs, vaccine protection may be more difficult in those areas of the world where cohabitation with animals occurs. We also need to have an accurate assessment of the rate of protection that follows natural infections. Is it realistic to try to achieve 90% protective efficacy with a vaccine if natural infections with these enteric pathogens only provide 60% or 70% protection? Subunit vaccines should be considered to be part of vaccine strategies, especially if maternal antibody interferes with the take of live vaccines. The constraints on development of new vaccines are not likely to come from molecular biology. The challenge remains whether the biology and immunology of rotavirus infections can be understood and exploited to permit effective vaccination. Recent advances in developing small animal models for evaluation of vaccine efficacy should facilitate future vaccine development and understanding of the protective immune response(s) (Ward et al. 1990b; Conner et al. 1993).

Animals↗

PubMed1998

Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk.

The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority. Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure. To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk. C. trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times. Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C. trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity. On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell. Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina. Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C. trachomatis. Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.

Chlamydia trachomatis↗

PubMed2026

Genome-Wide Identification and Characterization of the TBL Gene Family and Temporal Expression Dynamics During Powdery Mildew Infection in Cucumber (Cucumis sativus).

Cell-wall polysaccharide O-acetylation contributes to cell-wall assembly, organ development, and plant-pathogen interactions, but the cucumber TBL gene family remains poorly characterized. Here, 37 CsTBL genes were identified genome-wide and analyzed using phylogenetic, syntenic, conserved-motif, gene-structure, promoter, protein-structure, Gene Ontology, and transcriptome approaches, followed by RT-qPCR analysis after powdery mildew inoculation. All CsTBL proteins contained the conserved GDS and DxxH motifs, whereas accessory motifs and predicted structural features varied among clades. Intraspecific analysis identified dispersed, WGD/segmental, and tandem duplication categories, and cross-species synteny was more extensive with melon than with Arabidopsis. Homology-derived annotations associated CsTBL genes with cell-wall polysaccharide metabolism, Golgi/endomembrane compartments, and O-acetyltransferase activity, including six genes assigned to xylan O-acetyltransferase-related annotations. Expression profiling revealed tissue- and developmental-stage-dependent patterns, whereas the publicly available powdery mildew RNA-seq dataset provided descriptive temporal expression profiles in Podosphaera xanthii-inoculated samples. Independent RT-qPCR analysis using time-matched mock controls revealed distinct post-inoculation responses among six selected genes. Relative to the corresponding mock controls, CsTBL2 was consistently repressed; CsTBL15 showed transient induction at 1 dpi followed by repression; CsTBL24 exhibited a biphasic response; CsTBL25 was induced at all sampled post-inoculation time points; CsTBL26 showed progressive induction; and CsTBL30 reached its highest observed expression level at 3 dpi. Integrated functional annotation and expression evidence highlighted CsTBL26 as a priority candidate for further functional characterization, while CsTBL24 and CsTBL25 represented fruit-associated candidates with distinct powdery mildew responses; CsTBL30 remained an additional strongly infection-responsive candidate. These findings provide an evolutionary and expression-based framework for the functional characterization of the cucumber TBL gene family.

O-acetylation↗

PubMed2001

Prospects for reducing fumonisin contamination of maize through genetic modification.

Fumonisins (FB) are mycotoxins found in (italic)Fusarium verticillioides-infected maize grain worldwide. Attention has focused on FBs because of their widespread occurrence, acute toxicity to certain livestock, and their potential carcinogenicity. FBs are present at low levels in most field-grown maize but may spike to high levels depending on both the environment and genetics of the host plant. Among the strategies for reducing risk of FB contamination in maize supplied to the market, development and deployment of Fusarium ear mold-resistant maize germplasm is a high priority. Breeding for increased ear mold tolerance and reduced mycotoxin levels is being practiced today in both commercial and public programs, but the amount of resistance achievable may be limited due to complicated genetics and/or linkage to undesirable agronomic traits. Molecular markers can be employed to speed up the incorporation of chromosomal regions that have a quantitative effect on resistance (quantitative trait loci). Transgenic approaches to ear mold/mycotoxin resistance are now feasible as well. These potentially include genetically enhanced resistance to insect feeding, increased fungal resistance, and detoxification/prevention of mycotoxins in the grain. An example of the first of these approaches is already on the market, namely transgenic maize expressing Bacillus thuringiensis (Bt) toxin, targeted to the European corn borer. Some Bt maize hybrids have the potential to reduce FB levels in field-harvested grain, presumably through reduced feeding of Bt-susceptible insects in ear tissues. However, improved ear mold resistance per se is still an important goal, as the plant will still be vulnerable to noninsect routes of entry to (italic)Fusarium. A second approach, transgene-mediated control of the ability of Fusarium to infect and colonize the ear, could potentially be achieved through overexpression of specific antifungal proteins and metabolites, or enhancement of the plant's own defense systems in kernel tissues. This has not yet been accomplished in maize, although promising results have been obtained recently in other monocots versus other fungal and bacterial pathogens. Achieving reproducible and stable enhanced ear mold resistance under field conditions will be immensely challenging for biotechnologists. A third approach, transgene strategies aimed at preventing mycotoxin biosynthesis, or detoxifying mycotoxins in planta, could provide further protection for the grower in environments where FBs present a risk to the crop even when the maize is relatively resistant to Fusarium mold. In one example of such a strategy, enzymes that degrade FBs have been identified in a filamentous saprophytic fungus isolated from maize, and corresponding genes have been cloned and are currently being tested in transgenic maize.

Animals↗

PubMed2025

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by pathogenic variants in the SLC16A2 gene. Although most reported variants are found in protein-coding regions or adjacent junctions, structural variations (SVs) within non-coding regions have not been previously reported. METHODS: We investigated two male siblings with severe neurodevelopmental disorders and spasticity, who had remained undiagnosed for over a decade and were negative from exome sequencing, utilizing long-read HiFi genome sequencing. We conducted a comprehensive analysis including short-tandem repeats (STRs) and SVs to identify the genetic cause in this familial case. RESULTS: While coding variant and STR analyses yielded negative results, SV analysis revealed a novel hemizygous deletion in intron 1 of the SLC16A2 gene (chrX:74,460,691 - 74,463,566; 2,876 bp), inherited from their carrier mother and shared by the siblings. Determination of the breakpoints indicates that the deletion probably resulted from Alu/Alu-mediated rearrangements between homologous AluY pairs. The deleted region is predicted to include multiple transcription factor binding sites, such as Stat2, Zic1, Zic2, and FOXD3, which are crucial for the neurodevelopmental process, as well as a regulatory element including an eQTL (rs1263181) that is implicated in the tissue-specific regulation of SLC16A2 expression, notably in skeletal muscle and thyroid tissues. CONCLUSIONS: This report, to our knowledge, is the first to describe a non-coding deletion associated with AHDS, demonstrating the potential utility of long-read sequencing for undiagnosed patients. Although interpreting variants in non-coding regions remains challenging, our study highlights this region as a high priority for future investigation and functional studies.

Humans↗