A cluster of highly polymorphic dinucleotide repeats in intron 17b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene

A cluster of highly polymorphic dinucleotide repeats has been detected in intron 17b of the CFTR gene, 200 bp downstream from the preceding exon. At least 24 alleles, with sizes ranging from 7 to 56 units of a TA repeat, have been identified in a panel of 92 unrelated carriers of cystic fibrosis (CF). The common ones are those with 7, 30, and 31 dinucleotide units, with frequencies of .22, .19, and .12, respectively, among the non-CF chromosomes. Mendelian, codominant segregation of the alleles has been demonstrated in family studies, as expected. A less polymorphic dinucleotide (CA repeat) cluster has also been detected in a region 167 bp downstream from the TA repeat. The length of the CA repeat cluster varies from 11 to 17 dinucleotide units, and it appears to have an inverse relationship to that of the TA repeats. These dinucleotide repeats should be useful in genetic linkage studies, in counseling for CF families with unknown mutations, and in tracing the origins of the various mutant CF alleles.published_or_final_versio

Addition of Ammonium Thiocyanate Alters the Microstructure and Energetic Landscape of 2D/3D Perovskite Films

Mixtures of low-dimensional and 3D perovskite phases have attracted significant attention due to their improved stability with respect to purely 3D perovskites. One of the strategies to gain control over the complex crystallization of these 2D/3D perovskite films and obtain well-ordered thin films is through the additive engineering of the precursor solution. In this work, the influence of ammonium thiocyanate addition on the microstructural and optical properties of thin films of (PEA)2(MA)n−1PbnI3n+1 is investigated for different n values.</p

Genetic determination of exocrine pancreatic function in cystic fibrosis

We showed elsewhere that the pancreatic function status of cystic fibrosis (CF) patients could be correlated to mutations in the CF transmembrane conductance regulator (CFTR) gene. Although the majority of CF mutations- including the most common, ΔF508-strongly correlated with pancreatic insufficiency (PI), approximately 10% of the mutant alleles may confer pancreatic sufficiency (PS). To extend this observation, genomic DNA of 538 CF patients with well-documented pancreatic function status were analyzed for a series of known mutations in their CFTR genes. Only 20 of the 25 mutations tested were found in this population. They accounted for 84% of the CF chromosomes, with ΔF508 being the most frequent (71%), and the other mutations accounted for less than 5% each. A total of 30 different, complete genotypes could be determined in 394 (73%) of the patients. The data showed that each genotype was associated only with PI or only with PS, but not with both. This result is thus consistent with the hypothesis that PI and PS in CF are predisposed by the genotype at the CFTR locus; the PS phenotype occurs in patients who have one or two mild CFTR mutations, such as R117H, R334W, R347P, A455E, and P574H, whereas the PI phenotype occurs in patients with two severe alleles, such as ΔF508, ΔI507, Q493X, G542X, R553X, W1282X, 621 + 1G→T, 1717-1G→A, 556delA, 3659delC, I148T, G480C, V520F, G551D, and R560T.published_or_final_versio

Grain-Specific Transitions Determine the Band Edge Luminescence in Dion–Jacobson Type 2D Perovskites

The photophysics of 2D perovskites incorporating 1,4-phenylenedimethanammonium (PDMA) as spacer cations is studied. PDMAPbI4 and PDMASnI4 exhibit absorption and luminescence spectra dominated by excitonic transitions and an emission due to two different states. Low-temperature studies reveal a time-dependent red shift of 12 meV that is correlated with grain-specific luminescence spectra observed in optical micrographs. For the Pb-variant, grains of red-shifted and lower intensity band edge emission simultaneously exhibit a more pronounced luminescence from a broad defect-related band around 2 eV. This suggests the grain-specific emission to be related to local defects. These observations have important consequences for the understanding of luminescence of 2D perovskites, for which peak splitting of the band edge emission is a common, yet not completely resolved observation.</p

Ac-induced disruption of the doubleDs structure in tomato

The maize doubleDs element is stably maintained in the tomato genome. Upon the subsequent introduction of Ac into a plant containing doubleDs, disruption of the doubleDs structure and DNA rearrangements at the site of the doubleDs element were observed. No indications were obtained for excision of the complete doubleDs structure. The consequences of transactivation of doubleDs in these experiments are different from those described for transactivation of single Ds elements in tomato. The mechanisms by which such rearrangements could have occurred in tomato are discussed in relation to complex insertions containing doubleDs in maize

Emphysematous cholecystitis in a non-diabetic patient

A 47-year-old male was admitted at our emergency room with a 4-days history of acute abdominal pain, increased by inspiration. There was neither nausea nor vomiting. Physical examination revealed right upper quadrant and right flank tenderness. The patient had no diabetes mellitus. Laboratory tests showed a white-cell count at 15 x 109 cells/L (87% neutrophils), a CRP at 44,1 mg/dL, bilirubin at 1,9 mg/dL and ?GT at 114 U/L

Characterization of the Ac/Ds behaviour in transgenic tomato plants using plasmid rescue

We describe the use of plasmid rescue to facilitate studies on the behaviour of Ds and Ac elements in transgenic tomato plants. The rescue of Ds elements relies on the presence of a plasmid origin of replication and a marker gene selective in Escherichia coli within the element. The position within the genome of modified Ds elements, rescued both before and after transposition, is assigned to the RFLP map of tomato. Alternatively to the rescue of Ds elements equipped with plasmid sequences, Ac elements are rescued by virtue of plasmid sequences flanking the element. In this way, the consequences of the presence of an (active) Ac element on the DNA structure at the original site can be studied in detail. Analysis of a library of Ac elements, rescued from the genome of a primary transformant, shows that Ac elements are, infrequently, involved in the formation of deletions. In one case the deletion refers to a 174 bp genomic DNA sequence immediately flanking Ac. In another case, a 1878 bp internal Ac sequence is deleted

A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants

Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the β-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.

The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis

Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation