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In the present paper, an application of infrared thermography to inverse heat conduction problems is presented. The study involves the identification of conductive losses at the jaws of a tensile testing machine, which must be assessed in situ, because of variable fastening conditions of the specimen, inducing variable thermal resistances at the jaws. For this purpose, a photo-thermal technique has been developed to identify all the heat exchanges of the sample. An optical excitation, based on a halogen lamp projector, illuminates the specimen in situ on the tensile machine, while the radiative flux excitation is measured using a photodiode. The conductive fluxes are identified, transient and steady, then the equivalent exchange coefficients at the jaws. For this purpose, a direct numerical model by finite differences and an inverse procedure allow to estimate these exchange coefficients. The resolution of the inverse problem is based on the optimization by the conjugate gradient method, of a least square criterion between the temperatures measured by infrared thermography and the temperatures calculated from the direct model. [ABSTRACT FROM AUTHOR]

The mechanisms involved in the formation of subtelomeric rearrangements are now beginning to be elucidated. Breakpoint sequencing analysis of 1p36 rearrangements has made important contributions to this line of inquiry. Despite the unique architecture of segmental duplications inherent to human subtelomeres, no common mechanism has been identified thus far and different nonexclusive recombination–repair mechanisms seem to predominate. In order to gain further insights into the mechanisms of chromosome breakage, repair, and stabilization mediating subtelomeric rearrangements in humans, we investigated the constitutional rearrangements of 1p36. Cloning of the breakpoint junctions in a complex rearrangement and three non-reciprocal translocations revealed similarities at the junctions, such as microhomology of up to three nucleotides, along with no significant sequence identity in close proximity to the breakpoint regions. All the breakpoints appeared to be unique and their occurrence was limited to non-repetitive, unique DNA sequences. Several recombination- or cleavage-associated motifs that may promote non-homologous recombination were observed in close proximity to the junctions. We conclude that NHEJ is likely the mechanism of DNA repair that generates these rearrangements. Additionally, two apparently pure terminal deletions were also investigated, and the refinement of the breakpoint regions identified two distinct genomic intervals ~25-kb apart, each containing a series of 1p36 specific segmental duplications with 90–98% identity. Segmental duplications can serve as substrates for ectopic homologous recombination or stimulate genomic rearrangements. [ABSTRACT FROM AUTHOR]

Approximately one in 500 individuals carries a reciprocal translocation. Of the 121 monosomy 1p36 subjects ascertained by our laboratory, three independent cases involved unbalanced translocations of 1p and 9q, all of which were designated t(1;9)(p36.3;q34). These derivative chromosomes were inherited from balanced translocation carrier parents. To understand better the causes and consequences of chromosome breakage and rearrangement in the human genome, we characterized each derivative chromosome at the DNA sequence level and identified the junctions between 1p36 and 9q34. The breakpoint regions were unique in all individuals. Insertions and duplications were identified in two balanced translocation carrier parents and their unbalanced offspring. Sequence analyses revealed that the translocation breakpoints disrupted genes. This study demonstrates that apparently balanced reciprocal translocations in phenotypically normal carriers may have cryptic imbalance at the breakpoints. Because disrupted genes were identified in the phenotypically normal translocation carriers, caution should be exercised when interpreting data on phenotypically abnormal carriers with apparently balanced rearrangements that disrupt putative candidate genes.European Journal of Human Genetics (2006) 14, 1255–1262. doi:10.1038/sj.ejhg.5201710; published online 30 August 2006 [ABSTRACT FROM AUTHOR]

Although approximately 1 in 500 individuals carries a reciprocal translocation, little is known about the mechanisms that result in their formation. We analyzed the sequences surrounding the breakpoints in three unbalanced translocations of 1p and 9q, all of which were designated t(1;9)(p36.3;q34), to investigate the presence of sequence motifs that might mediate nonhomologous end joining (NHEJ). The breakpoint regions were unique in all individuals. Two of three translocations demonstrated insertions and duplications at the junctions, suggesting NHEJ in the formation of the rearrangements. No homology was identified in the breakpoint regions, further supporting NHEJ. We found translin motifs at the breakpoint junctions, suggesting the involvement of translin in the joining of the broken chromosome ends. We propose a model for balanced translocation formation in humans similar to transposition in bacteria, in which staggered nicks are repaired resulting in duplications and insertions at the translocation breakpoints. [ABSTRACT FROM AUTHOR]

Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)]. The clinical features of PSS can include developmental delay, mental retardation, multiple exostoses, parietal foramina, enlarged anterior fontanel, minor craniofacial anomalies, ophthalmologic anomalies, and genital abnormalities in males. We constructed a natural panel of 11p11.2-p13 deletions using cell lines from 10 affected individuals, fluorescence in situ hybridization (FISH), microsatellite analyses, and array-based comparative genomic hybridization (array CGH). We then compared the deletion sizes and clinical features between affected individuals. The full spectrum of PSS manifests when deletions are at least 2.1?Mb in size, spanning from D11S1393 to D11S1385/D11S1319 (44.6-46.7?Mb from the 11p terminus) and encompassing EXT2, responsible for multiple exostoses, and ALX4, causing parietal foramina. Yet one subject with parietal foramina whose deletion does not include ALX4 indicates that ALX4 in this subject may be rendered functionally haploinsufficient by a position effect. Based on comparative deletion mapping of eight individuals with the full PSS syndrome including mental retardation and two PSS families with no mental retardation, at least one gene related to mental retardation is likely located between D11S554 and D11S1385/D11S1319, 45.6-46.7?Mb from the 11p terminus.European Journal of Human Genetics (2005) 13, 528-540. doi:10.1038/sj.ejhg.5201366 [ABSTRACT FROM AUTHOR]

Structural chromosome abnormalities have aided in gene identification for over three decades. Delineation of the deletion sizes and rearrangements allows for phenotype/genotype correlations and ultimately assists in gene identification. In this report, we have delineated the precise rearrangements in four subjects with deletions, duplications, and/or triplications of 1p36 and compared the regions of imbalance to two cases recently published. Fluorescence in situ hybridization (FISH) analysis revealed the size, order, and orientation of the duplicated/triplicated segments in each subject. We propose a premeiotic model for the formation of these complex rearrangements in the four newly ascertained subjects, whereby a deleted chromosome 1 undergoes a combination of multiple breakage-fusion-bridge (BFB) cycles and inversions to produce a chromosome arm with a complex rearrangement of deleted, duplicated and triplicated segments. In addition, comparing the six subjects'rearrangements revealed a region of overlap that when triplicated is associated with craniosynostosis and when deleted is associated with large, late-closing anterior fontanels. Within this region are the MMP23A and -B genes. We show MMP23 gene expression at the cranial sutures and we propose that haploinsufficiency results in large, late-closing anterior fontanels and overexpression results in craniosynostosis. These data emphasize the important role of cytogenetics in investigating and uncovering the etiologies of human genetic disease, particularly cytogenetic imbalances that reveal potentially dosage-sensitive genes.European Journal of Human Genetics (2005) 13, 139-149. doi:10.1038/sj.ejhg.5201302 Published online 13 October 2004 [ABSTRACT FROM AUTHOR]

Axenic growth of a mixotrophic alga, Ochromonas sp., was compared in several inorganic and organic media, and in the presence of live bacteria under nutrient-replete and low-nutrient conditions. Axenic growth in the light was negligible in inorganic media with or without the addition of glucose. Addition of vitamins increased growth rate, but average cell size declined, resulting in no net increase in biomass. Supplementing axenic cultures with a more complex organic substrate resulted in moderate growth and higher maximal abundance (and biomass) than in the inorganic media with added vitamins. The absence of light did not greatly affect population growth rate in the presence of complex dissolved organic compounds, although cell size was significantly greater in the light than in the dark. The highest growth rates for the alga (up to 2.6 d?1) were measured in treatments containing live bacteria. Increases in cell number of Ochromonas sp. in the presence of bacterial prey were similar in the light and dark, although chloroplast and cell sizes differed. Bacterial abundance was reduced and dissolved phosphorus and ammonia were rapidly released in bacterized cultures in the light and dark, indicating high rates of bacterial ingestion and suggesting an inability of the alga to store or utilize N and P in excess of the quantities required for heterotrophic growth. Low-nutrient conditions in the presence of bacteria were promoted by adding glucose to stimulate bacterial growth and the uptake of N and P released by algal phagotrophy. Subsequent decreases in dissolved N and P following the addition of glucose corresponded to a second period of rapid growth of the alga in both light and dark. This result, combined with evidence for slow axenic growth of this strain, indicated that nutrient acquisition for this species in the presence of bacteria was accomplished primarily via ingestion of bacteria. [ABSTRACT FROM AUTHOR]

The realization that natural assemblages of planktonic bacteria may acquire a significant fraction of their nitrogen and phosphorus via the uptake of dissolved inorganic nutrients has modified our traditional view of these microorganisms as nutrient remineralizers in plankton communities. Bacterial uptake of inorganic nitrogen and phosphorus may place bacteria and phytoplankton in competition for growth-limiting nutrients, rather than in their traditional roles as the respective 'source' and 'sink' for these nutrients in the plankton. Bacterial nutrient uptake also implies that bacterivorous protozoa may play a pivotal role in the remineralization of these elements in the microbial loop. The overall contribution of bacterial utilization of inorganic nutrients to total nutrient uptake in the ocean is still poorly understood, but some generalizations are emerging with respect to the geographical areas and community physiological conditions that might elicit this behavior. [ABSTRACT FROM AUTHOR]