Distal deletion of the long arm of chromosome number 1 (q43-->qter) associated with severe mental retardation and a nonspecific dysmorphic syndrome.

A 6 8/12-year-old girl with severe mental retardation, multiple congenital malformations and a de novo distal deletion of the long arm of chromosome 1 [del 1 (q43-->qter)] is here described. A review of the reported patients does not allow to distinguish different phenotypes related to distal deletion 1q42 and/or 1q43.     

Isolation of early genes expressed in reproductive organs of the dioecious white campion (Silene latifolia) by subtraction cloning using an asexual mutant

The dioecious white campion (Silene latifolia) has been chosen as a working model for sexual development. In this species, sexual dimorphism is achieved through two distinct developmental blocks: inhibition of carpel development in male flowers, and early arrest of anther differentiation in female flowers. The combined advantages of the dioecious system and the availability of a sexual mutant lacking both male and female reproductive organs have been exploited in a molecular subtraction approach using male and asexual flower buds. This resulted in the cloning of 22 cDNA clones expressed in stamens at distinct stages of development. Fourteen of these clones corresponded to genes whose expression was detected in pre-meiotic stamens, a stage of development for which very little information is presently available. Furthermore, the absence of similarities with database sequences for ten clones suggests that they represent novel genes. Functional analysis of each clone will enable their positioning within the reproductive organ developmental pathway(s). In parallel, these clones are being exploited as developmental markers of early differentiation within the flower.     

Progress in cellular engineering of plants: biochemical and genetic assessment of selectable markers from cultured cells

Summary Recent availability of stable and well characterized selectable markers and ability to combine alien genomes parasexually have contributed to the development of molecular biology in higher plants, including gene expression and genetic manipulation.Several types of biochemical mutants (resistant to inhibitory concentrations of aminoacid(s) or aminoacid analogs as well as deficient for enzyme activity) have recently been isolated and characterized biochemically and genetically. Among them, mutants with alterations in the nitrogen and aminoacid metabolism, or in the activity of alcohol dehydrogenases are being used in the development of more efficient techniques of gene transfer.The manipulation of whole genomes by sexual or somatic cell fusion offers new potential in this field, but refinement of transfer techniques is desirable. The new set of selectable markers obtained through advanced cellular technology, as well as our ability to regenerate plants from manipulated cell lines are expected to play a major role in cellular engineering.     

Interstitial deletion (2)(p13p15)

Summary A dysmorphic 5-year-old girl with severe growth and mental deficiency was studied. She presented a de novo interstitial 2p deletion. Karyotype: 46,XX,del(2)(p13p15).     

Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36–54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351–727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia.     

Madelung deformity as a pathognomonic feature of the onycho-osteodysplasia syndrome.

On the occasion of the observation of the Onycho-osteo-dysplasia syndrome (HOOD syndrome--Nail-Patella syndrome) in a 4-generation family we were impressed by the presence of a Madelung deformity in the four examined family members. A critical review of the literature showed that a true Madelung deformity was present in a great number of previously reported patients but that no specific attention was given to this apparently important symptom.     

Mesenchymal stromal cell‐derived factors promote the colonization of collagen 3D scaffolds with human skin cells

The development of stem cell technology in combination with advances in biomaterials has opened new ways of producing engineered tissue substitutes. In this study, we investigated whether the therapeutic potential of an acellular porous scaffold made of type I collagen can be improved by the addition of a powerful trophic agent in the form of mesenchymal stromal cells conditioned medium (MSC‐CM) in order to be used as an acellular scaffold for skin wound healing treatment. Our experiments showed that MSC‐CM sustained the adherence of keratinocytes and fibroblasts as well as the proliferation of keratinocytes. Moreover, MSC‐CM had chemoattractant properties for keratinocytes and endothelial cells, attributable to the content of trophic and pro‐angiogenic factors. Also, for the dermal fibroblasts cultured on collagen scaffold in the presence of MSC‐CM versus serum control, the ratio between collagen III and I mRNAs increased by 2‐fold. Furthermore, the gene expression for α‐smooth muscle actin, tissue inhibitor of metalloproteinase‐1 and 2 and matrix metalloproteinase‐14 was significantly increased by approximately 2‐fold. In conclusion, factors existing in MSC‐CM improve the colonization of collagen 3D scaffolds, by sustaining the adherence and proliferation of keratinocytes and by inducing a pro‐healing phenotype in fibroblasts.     

Mesenchymal-to-Endothelial Transition in Kaposi Sarcoma: A Histogenetic Hypothesis Based on a Case Series and Literature Review

Objectives

Although several studies have been conducted regarding Kaposi sarcoma (KS), its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature.

Methods

In 15 cases of KSs diagnosed during 2000–2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF), COX-2, c-KIT, smooth muscle antigen (SMA), and stem cell surface marker CD105.

Results

Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs.

Conclusions

KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.     

The variability of different larch clone provenances on the response to the attack by its main pests and fungal diseases

A wide range of pests and diseases attacks larch, and over 3 years in an orchard in north-western Romania, the most frequently occurring were larch needle disease (Hypodermella laricis), the case-bearer (Coleophora laricella) and woolly adelgid (Adelges laricis) insects. Their attack on seven larch clones obtained through selection from different geographic populations from Romania was studied. To evaluate the attack intensity, four branches per tree were analysed in the upper, middle and lower third of the crowns in all cardinal directions. According to the position in the crown, a high attack intensity by H. laricis was recorded on the branches in the north direction. A high intensity of C. laricella attack was registered on the upper third of the crown, especially in the east, west and south directions. A positive relationship was identified between the damaged sprouts caused by the C. laricella and A. laricis attack. The differences among the reaction of the clones and the heritability coefficients illustrated that the response to the attacks had a strong genetic determinism, with resistance being clearly influenced by genotype. In addition to the identification of gene sources that are useful for larch breeding, this study offers technical information about the potential to develop efficient treatments based on the attacks on the tree crowns.     

Replication study of 34 common SNPs associated with prostate cancer in the Romanian population

Prostate cancer is the third‐most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature‐reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low‐grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.