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1.  A mutation in the receptor binding site of GDF5 causes Mohr‐Wriedt brachydactyly type A2 
Journal of Medical Genetics  2005;43(3):225-231.
Background
Brachydactyly type A2 (OMIM 112600) is characterised by hypoplasia/aplasia of the second middle phalanx of the index finger and sometimes the little finger. BDA2 was first described by Mohr and Wriedt in a large Danish/Norwegian kindred and mutations in BMPR1B were recently demonstrated in two affected families.
Methods
We found and reviewed Mohr and Wriedt's original unpublished annotations, updated the family pedigree, and examined 37 family members clinically, and radiologically by constructing the metacarpo‐phalangeal profile (MCPP) pattern in nine affected subjects. Molecular analyses included sequencing of BMPR1B, linkage analysis for STS markers flanking GDF5, sequencing of GDF5, confirmation of the mutation by a restriction enzyme assay, and localisation of the mutation inferred from the very recently reported GDF5 crystal structure, and by superimposing the GDF5 protein sequence onto the crystal structure of BMP2 bound to Bmpr1a.
Results
A short middle phalanx of the index finger was found in all affected individuals, but other fingers were occasionally involved. The fourth finger was characteristically spared. This distinguishes Mohr‐Wriedt type BDA2 from BDA2 caused by mutations in BMPR1B. An MCPP analysis most efficiently detected mutation carrier status. We identified a missense mutation, c.1322T>C, causing substitution of a leucine with a proline at amino acid residue 441 within the active signalling domain of GDF5. The mutation was predicted to reside in the binding site for BMP type 1 receptors.
Conclusion
GDF5 is a novel BDA2 causing gene. It is suggested that impaired activity of BMPR1B is the molecular mechanism responsible for the BDA2 phenotype.
doi:10.1136/jmg.2005.034058
PMCID: PMC2563247  PMID: 16014698
BDA2; brachydactyly; chondrogenesis; GDF5
2.  Differential effects of prolonged work on performance measures in self-paced speed tests. 
Time-related changes in the speeded performance of complex cognitive tasks are considered to arise from the combined effects of practice and mental fatigue. Here we explored the differential contributions of practice and fatigue to performance changes in a self-paced speeded mental addition and comparison task of about 50 min duration, administered twice within one week’s time. Performance measures included average response speed, accuracy, and response speed variability. The results revealed differential effects of prolonged work on different performance indices: Practice effects, being more pronounced in the first session, were reflected in an improvement of average response speed, whereas mental fatigue, occurring in both sessions, was reflected in an increase of response speed variability. This demonstrates that effects of mental fatigue on average speed of performance may be masked by practice effects but still be detectable in the variability of performance. Therefore, besides experimental factors such as the length and complexity of tasks, indices of response speed variability should be taken into consideration when interpreting different aspects of performance in self-paced speed tests.
doi:10.2478/v10053-008-0070-8
PMCID: PMC2916666  PMID: 20689668
reaction time; mental fatigue; sustained performance; time on task; practice effects
3.  Polymorphisms in the Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) Gene Are Associated with Peak Bone Mass in Non-sedentary Men: Results from the Odense Androgen Study 
Calcified Tissue International  2007;81(6):421-429.
Purpose
To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men.
Methods
The Odense Androgen Study (OAS) is a population-based study comprising 783 Caucasian men aged 20-30 years. Genotyping was performed using real-time polymerase chain reaction (PCR) or fluorescence polarization. Bone mineral density (BMD) measurements were performed using dual-energy X-ray absorptiometry.
Results
The CC, CT, and TT genotypes in Ala1330Val were found in 75.6%, 21.8%, and 2.6% of the participants, respectively. Similarly, the GG, GA, and AA genotypes of Val667Met were found in 89.7%, 9.8%, and 0.5%, respectively. For the Ala1330Val polymorphism, no significant differences between the genotypes were found regarding BMD in the overall study population. However, when analysis was restricted to non-sedentary men (n = 589), a significant association between the number of T-alleles and BMD in the spine and whole body were found. Each copy of the T-allele changed the Z-score of the spine by (median and 95% confidence interval) −0.21 [95% CI: −0.40; −0.03] (p < 0.02). Analysis suggested an association between the AA genotype in the Val667Met polymorphism and increased body height and decreased BMD of the femoral neck; however, no significant gene-dose effect of the A-allele could be demonstrated in the whole population. When the analysis was restricted to non-sedentary subjects, however, each number of A-alleles was associated with a change in Z-score of −0.26 [95% CI: −0.51; −0.01] (p = 0.04). No further significant results emerged with haplotype analysis.
Conclusion
The Ala1330Val and Val667Met polymorphisms in the LRP5 gene are significantly associated with peak bone mass in physically active men.
doi:10.1007/s00223-007-9088-z
PMCID: PMC2151961  PMID: 18058054
Association; Bone mineral density; Low-density lipoprotein receptor-related protein 5; Men; Polymorphisms
4.  Optimization of Bacteriocin Release Protein (BRP)-Mediated Protein Release by Escherichia coli: Random Mutagenesis of the pCloDF13-Derived BRP Gene To Uncouple Lethality and Quasi-Lysis from Protein Release 
Bacteriocin release proteins (BRPs) can be used for the release of heterologous proteins from the Escherichia coli periplasm into the culture medium. However, high-level expression of BRP causes apparent lysis of the host cells in liquid cultures (quasi-lysis) and inhibition of growth on broth agar plates (lethality). To optimize BRP-mediated protein release, the pCloDF13 BRP gene was subjected to random mutagenesis by using PCR techniques. Mutated BRPs with a strongly reduced capacity to cause growth inhibition on broth agar plates were selected, analyzed by nucleotide sequencing, and further characterized by performing growth and release experiments in liquid cultures. A subset of these BRP derivatives did not cause quasi-lysis and had only a small effect on growth but still functioned in the release of the periplasmic protein β-lactamase and the periplasmic K88 molecular chaperone FaeE and in the release of the bacteriocin cloacin DF13 into the culture medium. These BRP derivatives can be more efficiently used for extracellular production of proteins by E. coli than can the original BRP.
PMCID: PMC106056  PMID: 9464372
5.  Instability of lymphocyte chromosomes in a girl with Rothmund-Thomson syndrome. 
Journal of Medical Genetics  1994;31(7):570-572.
Rothmund-Thomson syndrome is a rare autosomal recessive syndrome characterised by poikiloderma of the face and extremities, alopecia, short stature, and skeletal defects. We report a patient with the characteristic features of Rothmund-Thomson syndrome who also had lymphocyte chromosome abnormalities. She has a small flat face with short palpebral fissures and micrognathia together with severe skeletal abnormalities of the upper extremities with absence of both radii, short dysmorphic ulnae, a rudimentary right thumb, and aplasia of the left thumb. She also has anal atresia with a rectovaginal fistula. From the age of 3 months she developed poikiloderma skin changes on the face and extensor surfaces of the extremities. Mental development seems to be normal. Lymphocyte chromosomes in the neonatal period showed an unidentified marker chromosome in eight of a total of 32 cells. A repeat analysis at the age of 10 months showed three abnormal cells out of 100 analysed: 47,XX,-7,+i(7q),+7p, 46,XX,t(3;18)(p14.2;q22), and 49,XX,+del(3)(p11.2),+mar,+mar. A skin biopsy from an affected area showed poor growth and five of 48 cells analysed had structural abnormalities. The father had one of 48 cells with an additional marker chromosome and two cells with different 7;14 translocations. The abnormal chromosome complements in lymphocytes indicate that there may be in vivo chromosome instability in Rothmund-Thomson syndrome.
Images
PMCID: PMC1049982  PMID: 7966195
6.  Kinetics of human connecting peptide in normal and diabetic subjects. 
Journal of Clinical Investigation  1978;62(1):197-203.
The metabolic clearance rate (MCR) of synthetic human connecting peptide (C-peptide) was measured with a single-dose injection technique in six normal and seven diabetic subjects and with a constant infusion technique in one normal subject. The MCR of C-peptide did not differ in normal subjects (4.4 ml/min per kg; range, 3.7-4.9) and in diabetic subjects (4.7 ml/min per kg; range, 3.7-5.8). Employment of both techniques in one subject gave similar MCR. The average half-life of C-peptide in plasma calculated from the last 1-h period of the single-dose injection studies was longer in the insulin-dependent diabetics (42.5 min; range, 39.4-48.5) than in the normal subjects (33.5 min; range, 24.9-45.3). These results indicate that the beta-cell secretory capacity of normal and insulin-dependent diabetic subjects can be compared by measuring the C-peptide concentration in peripheral venous plasma. The difference in the half-life of C-peptide in plasma between diabetics and normals suggests an altered kinetics of the disappearance of the peptide, while the overall metabolism, as expressed by the MCR, is similar.
PMCID: PMC371754  PMID: 659633
10.  Use of the Scanning Electron Microscope for Viewing Bacteria in Soil 
Applied Microbiology  1968;16(6):932-934.
Scanning electron microscopy was used for viewing Bacillus cereus and Staphylococcus aureus in three different soils. Both organisms were detected in the test soils at an approximate concentration of 107 cells per gram of soil; theoretically, the minimal number of microorganisms required for detection with the scanning electron microscope technique was between 107 and 1010 cells per gram of soil. Because the concentration of cells was critical, the use of scanning electron microscopy as an extraterrestrial life detection instrument would be limited with soils containing more than 107 bacteria per gram of soil.
Images
PMCID: PMC547556  PMID: 4969663
11.  Survival of Microorganisms in a Simulated Martian Environment 
Applied Microbiology  1967;15(2):285-291.
The effects of moisture and oxygen concentration on germination of Bacillus cereus and B. subtilis var. niger spores were investigated in a simulated Martian environment. Less moisture was required for germination than for vegetative growth of both organisms. A daily freeze-thaw cycle lowered moisture requirements for spore germination and vegetative growth of both organisms, as compared with a constant 35 C environment. Oxygen had a synergistic effect by lowing the moisture requirements for vegetative growth, and possibly germination, of both organisms. Oxygen was not required for spore germination of either organism, but was required for vegetative growth of B. subtilis and for sporulation of both organisms.
Images
PMCID: PMC546892  PMID: 4961769
12.  Survival of Microorganisms in a Simulated Martian Environment 
Applied Microbiology  1964;12(3):215-218.
Survival of Bacillus subtilis var. globigii in a simulated Martian environment was demonstrated. Previous contact with the simulated Martian soil or atmosphere reduced germination or outgrowth of unheated spores, or both. Inoculation into simulated Martian soil and then flushing with a simulated Martian atmosphere were lethal to both vegetative cells and spores. After one diurnal temperature cycle (26 to -60 C), the majority of of cells present were spores. No further effect of the diurnal cycle on survival was noted in any of the experimental samples.
PMCID: PMC1058102  PMID: 14170958

Results 1-12 (12)