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The translocation-associated tox1 locus of Cochliobolus heterostrophus is two genetic elements on two different chromosomes.

Previously, Tox1 was defined as a single genetic element controlling the difference between races of Cochliobolus heterostrophus: race T is highly virulent on T-cytoplasm corn and produces the polyketide T-toxin; race O is weakly virulent and does not produce T-toxin. Here we report that Tox1 is two loci, Tox1A and Tox1B, on two different chromosomes. Evidence for two loci derives from: (1) the appearance of 25% Tox+ progeny in crosses between induced Tox1(-) mutants, one defective at Tox1A, the other at Tox1B; (2) the ability of Tox1A- + Tox1B- heterokaryons to complement for T-toxin production; and (3) electrophoretic karyotypes proving that Tox1(-) mutations are physically located on two different chromosomes. Data showing Tox1 as a single genetic element are reconciled with those proving it is two loci by the fact that Tox1 is inseparably linked to the breakpoints of a reciprocal translocation; the translocation results in a four-armed linkage group. In crosses where the translocation is heterozygous (i.e., race T by race O), all markers linked to the four-armed intersection appear linked to each other; in crosses between induced Tox1(-) mutants, complications due to the translocation are eliminated and the two loci segregate independently.

Ascomycota↗

Gene expression profile analysis by DNA microarrays: promise and pitfalls.

DNA microarrays represent a technological intersection between biology and computers that enables gene expression analysis in human tissues on a genome-wide scale. This application can be expected to prove extremely valuable for the study of the genetic basis of complex diseases. Despite the enormous promise of this revolutionary technology, there are several issues and possible pitfalls that may undermine the authority of the microarray platform. We discuss some of the conceptual, practical, statistical, and logistical issues surrounding the use of microarrays for gene expression profiling. These issues include the imprecise definition of normal in expression comparisons; the cellular and subcellular heterogeneity of the tissues being studied; the difficulty in establishing the statistically valid comparability of arrays; the logistical logjam in analysis, presentation, and archiving of the vast quantities of data generated; and the need for confirmational studies that address the functional relevance of findings. Although several complicated issues must be resolved, the potential payoff remains large.

Gene Expression Profiling↗

Molecular targets of vertebrate segmentation: two mechanisms control segmental expression of Xenopus hairy2 during somite formation.

Vertebrate hairy genes are expressed in patterns thought to be readouts of a "segmentation clock" in the presomitic mesoderm. Here we use transgenic Xenopus embryos to show that two types of regulatory elements are required to reconstitute the segmental pattern of Xenopus hairy2. The first is a promoter element containing two binding sites for Xenopus Su(H), a transcriptional activator of Notch target genes. The second is a short sequence in the hairy2 3' untranslated region (UTR), which most likely functions posttranscriptionally to modulate hairy2 RNA levels. 3' UTRs of other hairy-related, segmentally expressed genes can substitute for that of hairy2. Our results demonstrate a novel mechanism regulating the segmental patterns of Notch target genes and suggest that vertebrate segmentation requires the intersection of two regulatory pathways.

3' Untranslated Regions↗

Reactive oxygen species as mediators of cellular senescence.

Aging has often been viewed as a random process arising from the accumulation of both genetic and epigenetic changes. Increasingly, the notion that aging is a stochastic process is being supplanted by the concept that maximum lifespan of an organism is tightly regulated. This knowledge has led to a growing overlap between classical signal transduction paradigms and the biology of aging. We review certain specific examples where these seemingly disparate disciplines intersect. In particular, we review the concept that intracellular reactive oxygen species function as signalling molecules and that oxidants play a central role as mediators of cellular senescence.

Animals↗

Sex as a modifier of genetic risk for type 1 diabetes.

Sex differences influence the pathogenesis of type 1 diabetes (T1D), yet most genetic studies have treated sex as a control covariate rather than a dynamic effect modifier. Sex influences immune cell behaviour, including CD4+ and CD8+ T cell activation, regulatory T cell stability, B cell autoantibody production, dendritic cell priming and monocyte/macrophage inflammation. Underlying mechanisms include hormone-responsive enhancers, X-escape gene dosage and sex-biassed chromatin states, intersecting with T1D-associated variants to produce sex-specific immune phenotypes. These insights help explain regional variation in sex ratios of T1D incidence, such as male predominance in high-risk populations and female excess in low-risk populations. Biological sex shapes T1D risk across multiple layers, including polygenic load; environmental exposures such as vitamin D deficiency and enteroviral infection; and sex-specific hormonal, chromosomal and epigenetic influences. An integrative G × E × S (genetic × environmental × sex-specific) liability-threshold framework is thus supported. Clinical and translational implications include developing sex-specific polygenic risk scores, biomarker panels and interventional strategies targeting pathways such as hormone signalling, vitamin D metabolism and the microbiome. Future multi-omic, longitudinal studies are warranted to test genotype-sex interactions, integrate sex as a core effect modifier and enable precision prevention and treatment of T1D in both males and females.

Humans↗

Nucleotide-binding-oligomerization domain proteins and toll-like receptors: sensors of the inflammatory bowel diseases' microbial environment.

PURPOSE OF REVIEW: Chronic inflammatory bowel diseases appear to result from inappropriate immune responses driven by apparently normal intestinal microflora in genetically susceptible hosts. This review focuses on recently described mechanisms balancing toll-like receptor and nucleotide-binding-oligomerization domain activation in the face of ubiquitous enteric flora. RECENT FINDINGS: Toll-like receptor and nucleotide-binding-oligomerization domain signaling plays an integral role in the close collaboration between the intestinal epithelial cell monolayer and adjacent mucosal immune cells. Pathways activated by functional cytosolic nucleotide-binding-oligomerization domain proteins appear to interact with those mediated by membrane-associated toll-like receptors in the innate and adaptive immune defense against intra-and extracellular pathogens. Nucleotide-binding-oligomerization domain-mediated signaling may also control toll-like receptor-induced proinflammatory pathways. SUMMARY: Intersections between toll-like receptor and nucleotide-binding-oligomerization domain pathways may exist to refine the host immune response to pathogens and prevent undesired immune stimulation driven by the intestinal microbiota. Deficient toll-like receptor and nucleotide-binding-oligomerization domain function due to genetic variability is associated with an increased susceptibility to the development of inflammatory bowel disease.

Bacteria↗

Intersecting pools and their potential application in testing donated blood for viral genomes.

Amplification assays for viral genomes are at present too expensive and cumbersome to be applied to individual blood donations. Through constructing interesting pools of specimens, however, it may be possible to screen as a single process large numbers of units for several low prevalence viruses using relatively few tests. The preparation of the intersecting pools that would be required is explained in this paper. If test sensitivity and specificity were adequate, the testing of these pools would permit timely release of components that had the security of genetic testing added to current serological screening programmes. The method also makes screening for other viruses feasible.

Blood↗

Genetic diversity of isolates of Glomus mosseae from different geographic areas detected by vegetative compatibility testing and biochemical and molecular analysis.

We detected, for the first time, the occurrence of vegetative incompatibility between different isolates of the arbuscular mycorrhizal fungal species Glomus mosseae. Vegetative compatibility tests performed on germlings belonging to the same isolate showed that six geographically different isolates were capable of self-anastomosing, and that the percentage of hyphal contacts leading to fusions ranged from 60 to 85%. Successful anastomoses were characterized by complete fusion of hyphal walls, protoplasm continuity and occurrence of nuclei in the middle of hyphal bridges. No anastomoses could be detected between hyphae belonging to different isolates, which intersected without any reaction in 49 to 68% of contacts. Microscopic examinations detected hyphal incompatibility responses in diverse pairings, consisting of protoplasm retraction from the tips and septum formation in the approaching hyphae, even before physical contact with neighboring hyphae. Interestingly, many hyphal tips showed precontact tropism, suggesting that specific recognition signals may be involved during this stage. The intraspecific genetic diversity of G. mosseae revealed by vegetative compatibility tests was confirmed by total protein profiles and internal transcribed spacer-restriction fragment length polymorphism profiles, which evidenced a higher level of molecular diversity between the two European isolates IMA1 and BEG25 than between IMA1 and the two American isolates. Since arbuscular mycorrhizal fungi lack a tractable genetic system, vegetative compatibility tests may represent an easy assay for the detection of genetically different mycelia and an additional powerful tool for investigating the population structure and genetics of these obligate symbionts.

DNA, Fungal↗

Engineering the surface properties of synthetic gene delivery vectors.

Synthetic gene delivery vehicles are a highly promising approach to gene delivery; however, several problems must still be overcome before they can begin to enjoy dinical success. A number of these problems can be addressed by engineering and optimizing the properties of the vector surface, the component of the particle that interacts and "communicates" with tissues and cells during the delivery process. Surfaces must be engineered to satisfy two ostensibly conflicting constraints: the ability to interact specifically with a target cell while avoiding nonspecific protein interactions, particularly with components of the immune system. We summarize progress that has been made in both these areas and discuss several approaches where the intersection of biological and chemical solutions promises to significantly advance the engineering of synthetic vehicles.

Animals↗

Genetics of natural populations, XLIII. Further studies on rates of dispersal of Drosophila pseudoobscura and its relatives.

The amount of gene flow among local populations of a species is determined by the dispersal capacity of that species. Population samples of Drosophila pseudoobscura, D. persimilis, D. azteca, and D. miranda were collected, marked with ultraviolet fluorescent dusts, and released as soon as possible after capture. One and two days after release, recaptures were made on baits placed at 40-meter intervals in straight lines intersecting the release point. On alternative days, the baits were placed in North-South or in East-West directions. The distribution of the recaptured flies about the release point is very nearly normal. No significant differences between the dispersal rates of the four species are observed; however, males disperse slightly further than females. The variances averaged 50,822 m2 on the first day and 80,048 m2 on the second day and the estimated mean distances from the release point averaged 263 m and 361 m respectively. The genetic implications of the results are discussed.

Animals↗

Genome-wide analysis of hydrogen peroxide-regulated gene expression in Arabidopsis reveals a high light-induced transcriptional cluster involved in anthocyanin biosynthesis.

In plants, reactive oxygen species and, more particularly, hydrogen peroxide (H(2)O(2)) play a dual role as toxic by-products of normal cell metabolism and as regulatory molecules in stress perception and signal transduction. Peroxisomal catalases are an important sink for photorespiratory H(2)O(2). Using ATH1 Affymetrix microarrays, expression profiles were compared between control and catalase-deficient Arabidopsis (Arabidopsis thaliana) plants. Reduced catalase levels already provoked differences in nuclear gene expression under ambient growth conditions, and these effects were amplified by high light exposure in a sun simulator for 3 and 8 h. This genome-wide expression analysis allowed us to reveal the expression characteristics of complete pathways and functional categories during H(2)O(2) stress. In total, 349 transcripts were significantly up-regulated by high light in catalase-deficient plants and 88 were down-regulated. From this data set, H(2)O(2) was inferred to play a key role in the transcriptional up-regulation of small heat shock proteins during high light stress. In addition, several transcription factors and candidate regulatory genes involved in H(2)O(2) transcriptional gene networks were identified. Comparisons with other publicly available transcriptome data sets of abiotically stressed Arabidopsis revealed an important intersection with H(2)O(2)-deregulated genes, positioning elevated H(2)O(2) levels as an important signal within abiotic stress-induced gene expression. Finally, analysis of transcriptional changes in a combination of a genetic (catalase deficiency) and an environmental (high light) perturbation identified a transcriptional cluster that was strongly and rapidly induced by high light in control plants, but impaired in catalase-deficient plants. This cluster comprises the complete known anthocyanin regulatory and biosynthetic pathway, together with genes encoding unknown proteins.

Anthocyanins↗

Bidirectional sticker systems.

We introduce two-sided sticker systems, the two-sided variant of a computability model introduced as an abstraction of Adleman's style of DNA computing and of the matching of the so-called Watson-Crick complements. Several types of sticker systems are shown to have the same power as regular grammars, one variant is found to represent the linear languages, and another one is proved to be able to represent any recursively enumerable language. From this result we infer that any recursively enumerable language can be represented as the projection of the intersection of two minimal linear languages.

Base Composition↗

[Advances in studies on genetically engineered microorganism ecology].

Genetically engineered microorganism ecology has been one of main research contents in microorganism molecular ecology. Along with the introduction of molecular marker and molecular biology, traditional microorganism ecology has been developed; therefore, it is possible to study the relationship between GEM and environment, environmental microorganism under molecular level. The GEM ecology has become a new and intersection borderline discipline, related to molecular biology, microbiology, ecology and so on. Moreover, it brought forward that the prosecution of the research on the transgenic organism ecology and the risk assessment, and the foundation of checking means and valuating standard that adapt to the situation of China could help to the development of GEM ecology in China.

Ecology↗

Cardiovascular disease genetics: a long and winding road.

PURPOSE OF REVIEW: This review has two major goals. The first goal is to raise some of the methodological problems associated with studying the genetics of complex disorders, specifically cardiovascular diseases. The second is to update the reader with the most recent findings in the area of genotype-phenotype associations as well as the interaction between genetic factors and cardiovascular disease risk markers, with emphasis on those related to lipid metabolism. RECENT FINDINGS: In terms of new information, three topics are presented: (1) new findings related to classical candidate genes, such as apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase; (2) recent reports related to new loci that have joined the growing list of cardiovascular disease candidate genes (i.e. ATP-binding cassette transporters A1 and C6, peroxisome proliferator activated receptor alpha, interleukin-6); and (3) studies showing that multiple genes appear to be at the intersection of several age-related disorders such as cardiovascular disease, neurological disorders and osteoporosis (i.e. apolipoprotein E, vitamin D receptor, matrix Gla protein, peroxisome proliferator activated receptor gamma, angiotensin-converting enzyme, estrogen receptor, androgen receptor, methylenetetrahydrofolate reductase). SUMMARY: The dramatic increase in our ability to carry out genotyping is creating a tremendous wealth of information in terms of associations between genetic markers and biochemical or clinical phenotypes. Increased attention, however, should be placed on study design and replication of findings. This should also be facilitated by the inclusion of multiple markers per loci in order to provide a more precise definition of the alleles associated with the phenotypes of interest. Moreover, given the fact that most of the phenotypes are equally affected by genetic and environmental factors, studies should emphasize the analyses of their interaction.

Cardiovascular Diseases↗

Delayed abscission and shorter Internodes correlate with a reduction in the ethylene receptor LeETR1 transcript in transgenic tomato.

Stable transformation of tomato (Lycopersicon esculentum cv Ailsa Craig) plants with a construct containing the antisense sequence for the receiver domain and 3'-untranslated portion of the tomato ethylene receptor (LeETR1) under the control of an enhanced cauliflower mosaic virus 35S promoter resulted in some expected and unexpected phenotypes. In addition to reduced LeETR1 transcript levels, the two most consistently observed phenotypes in the transgenic lines were delayed abscission and reduced plant size. Fruit coloration and softening were essentially unaffected, and all the seedlings from first generation seed displayed a normal triple response to ethylene. Two independent lines with a single copy of the transgene and reduced LeETR1 transcript accumulation were selected for detailed phenotypic analysis of second generation (R1) plants. Delayed abscission, shorter internode length, and reduced auxin movement all correlated with the presence of the transgene and the degree of reduced LeETR1 transcript accumulation. No significant differences were noted for fruit coloration or fruit softening on R1 plants and all seedlings from R1 and R2 seed displayed a normal triple response. LeETR2 transcript accumulation was only slightly reduced in the R1 plants compared with azygous plants, and LeETR3 (NR) transcript levels appeared to be unaffected by the transgene. We propose that ethylene signal transduction occurs through parallel paths that partially intersect to regulate shared ethylene responses.

Biological Transport↗

Integrated microfluidic electrophoresis system for analysis of genetic materials using signal amplification methods.

An isothermal signal amplification technique for specific DNA sequences, known as cycling probe technology (CPT), was performed within a microfluidic chip. The presence of DNA from methicillin-resistant Staphylococcus aureus was determined by signal amplification of a specific DNA sequence. The microfluidic device consisted of four channels intersecting to mix the sample and reagents within 55 s, as they were directed toward the reactor coil by electrokinetic pumping. The 160-nL CPT reactor occupied approximately 220 mm2. Gel-free capillary electrophoresis separation of the biotin- and fluorescein-labeled probe from the probe fragments was performed on-chip following the on-chip reaction. An off-chip CPT reaction, with on-chip separation gave a detection limit of 2 fM (0.03 amol) target DNA and an amplification factor of 85,000. Calibration curves, linear at <5% probe fragmentation, obeyed a power law relationship with an argument of 0.5 [target] at higher target DNA concentrations for both on-chip and off-chip CPT reaction and analysis. An amplification factor of 42,000 at 250 fM target (25,000 target molecules) was observed on-chip, but the reaction was approximately 4 times less sensitive than off-chip under the conditions used. Relative SD values for on-chip CPT were 0.8% for the peak migration times, 9% for the area of intact probe peak, and 8% for the fragment/probe peak area ratio.

DNA↗

Genetic- or transforming growth factor-beta 1-induced changes in epidermal peroxisome proliferator-activated receptor beta/delta expression dictate wound repair kinetics.

Advances in wound care are of great importance in clinical injury management. In this respect, the nuclear receptor peroxisome proliferator-activated receptor (PPAR)beta/delta occupies a unique position at the intersection of diverse inflammatory or anti-inflammatory signals that influence wound repair. This study shows how changes in PPARbeta/delta expression have a profound effect on wound healing. Using two different in vivo models based on topical application of recombinant transforming growth factor (TGF)-beta1 and ablation of the Smad3 gene, we show that prolonged expression and activity of PPARbeta/delta accelerate wound closure. The results reveal a dual role of TGF-beta1 as a chemoattractant of inflammatory cells and repressor of inflammation-induced PPARbeta/delta expression. Also, they provide insight into the so far reported paradoxical effects of the application of exogenous TGF-beta1 at wound sites.

Administration, Topical↗

[Psychotherapeutic methods beyond the scope of individual schools of psychotherapy].

The author discusses four basic theoretical methodological approaches elaborated by H. Seiffert and R. Lay which were recommended by R. Vogt and in particular P. Hahn for medicine and psychology. The author explains also primary diagnostic methods used in psychotherapy. Due to the aspect of medical anthropology these basic methods are considered aspects of genetic epidemiology and at the same time as theoretical guidelines for the diagnosis and therapy of anthropological dimensions of diseases. Traditional combination of all diagnostic methods from the "clinical aspect" is then substituted by specific differentiation at the point of intersection of objective and subjective facts concerning the disease.

Humans↗