Search PubMed⌕ Search

Biomedical subjects

Peter Nilsson

Publications and source records attributed to Peter Nilsson.

At least 55 records · Page 3Linked to original sources
PubMed2004

A high-resolution transcript profile across the wood-forming meristem of poplar identifies potential regulators of cambial stem cell identity.

Plant growth is the result of cell proliferation in meristems, which requires a careful balance between the formation of new tissue and the maintenance of a set of undifferentiated stem cells. Recent studies have provided important information on several genetic networks responsible for stem cell maintenance and regulation of cell differentiation in the apical meristems of shoots and roots. Nothing, however, is known about the regulatory networks in secondary meristems like the vascular cambium of trees. We have made use of the large size and highly regular layered organization of the cambial meristem to create a high-resolution transcriptional map covering 220 microm of the cambial region of aspen (Populus tremula). Clusters of differentially expressed genes revealed substantial differences in the transcriptomes of the six anatomically homogenous cell layers in the meristem zone. Based on transcriptional and anatomical data, we present a model for the position of the stem cells and the proliferating mother cells in the cambial zone. We also provide sets of marker genes for different stages of xylem and phloem differentiation and identify potential regulators of cambial meristem activity. Interestingly, analysis of known regulators of apical meristem development indicates substantial similarity in regulatory networks between primary and secondary meristems.

Cell Differentiation↗
PubMed2004

Dioxygen-promoted regioselective oxidative heck arylations of electron-rich olefins with arylboronic acids.

Arylations of electron-rich heteroatom-substituted olefins were performed with arylboronic acids. This appears to constitute the first example of palladium(II)-catalyzed internal Heck arylations. The novel protocol exploits oxygen gas for environmentally benign reoxidation and a stable 1,10-phenanthroline bidentate ligand to promote the palladium(II) regeneration and to control the regioselectivity. Internal arylation is strongly favored with electron-rich arylboronic acids. DFT calculations support a charge-driven selectivity rationale, where phenyls substituted with electron-donating groups prefer the electron-poor alpha-carbon of the olefin. Experiments, verified by calculations, confirm the cationic nature of the catalytic route. This Heck methodology provides a facile and mild access to functionalized enamides. Controlled microwave heating and increased oxygen pressure were used to further reduce the reaction time to 1 h.

Journal Article↗
PubMed2004

Microwave-promoted and chelation-controlled double arylations of terminal olefinic carbon of vinyl ethers.

Herein we report a rapid, palladium-catalyzed terminal diarylation of the chelating olefin N,N-dimethyl(2-ethenyloxy)ethanamine under noninert conditions utilizing controlled microwave heating as a convenient energy source. Among the aryl bromides examined, both electron-rich and electron-poor substrates were demonstrated to furnish useful yields after only 10-120 min of directed microwave heating at 160-200 degrees C. The good terminal regioselectivity suggests that the precatalyst (Herrmann's palladacycle) serves as a source of weakly coordinated palladium(0) in the investigated high-temperature Heck process.

Journal Article↗
PubMed2004

Three replication origins in Sulfolobus species: synchronous initiation of chromosome replication and asynchronous termination.

Chromosome replication origins were mapped in vivo in the two hyperthermophilic archaea, Sulfolobus acidocaldarius and Sulfolobus solfataricus, by using microarray-based marker frequency analysis. Bidirectional replication was found to be initiated in near synchrony from three separate sites in both organisms. Two of the three replication origins in each species were located in the vicinity of a cdc6/orc1 replication initiation gene, whereas no known replication-associated gene could be identified near the third origin in either organism. In contrast to initiation, replication termination occurred asynchronously, such that certain replication forks continued to progress for >40 min after the others had terminated. In each species, all replication forks advanced at similar DNA polymerization rates; this was found to be an order of magnitude below that displayed by Escherichia coli and thus closer to eukaryotic elongation rates. In S. acidocaldarius, a region containing short regularly spaced repeats was found to hybridize aberrantly, as compared to the rest of the chromosome, raising the possibility of a centromere-like function.

Chromosomes↗
PubMed2004

A transcriptional timetable of autumn senescence.

BACKGROUND: We have developed genomic tools to allow the genus Populus (aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag (EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. RESULTS: On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree (Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. CONCLUSIONS: We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.

Aging↗
PubMed2004

Microarray technology for identification and distinction of hantaviruses.

DNA microarrays combine high-precision technology with advanced molecular biology to achieve high-throughput screening of DNA fragments. In this study, we investigated the potential of the cDNA microarray technique to identify and discriminate PCR derived amplicons from genetically highly similar viruses. The wide range of sequence variation among hantaviruses makes them suitable as a model for this purpose. The hantaviruses, carried by rodents, cause several hundred thousand cases of severe human disease every year in many parts of the world. A hantavirus-specific microarray, including DNA fragments from 12 viral isolates of six different hantaviruses, was designed. The S and M genome segments were represented by 500-nucleotide overlapping and 250-nucleotide non-overlapping fragments. A considerable ability to distinguish between different hantaviruses was demonstrated using a novel analysis method. Even different isolates of a single virus, were identified correctly despite 90% sequence similarity. The distinction ability was accompanied by a tolerance for smaller sequence differences, which makes the microarray suitable for testing samples containing unknown viruses. Viral genetic material found in samples from the lungs of bank voles caught in the wild was identified precisely, which demonstrated further the potential for this technology.

Animals↗
PubMed2004

Zygoma fixture in the management of advanced atrophy of the maxilla: technique and long-term results.

Despite refinements in surgical technique, including bone grafting and sophisticated prosthetic reconstructions, there are limitations to what can be achieved with bone-anchored fixed prostheses in patients with advanced atrophy of the maxillae. A new approach was suggested by a long-term study on onlay bone grafting and simultaneous placement of a fixture based on a new design: the zygoma fixture, and the aim of this study was to assess its potential. Twenty-eight consecutive patients with severely resorbed edentulous maxillae were included, 13 of whom had previously had multiple fixture surgery in the jawbone that had failed. A total of 52 zygoma fixtures and 106 conventional fixtures were installed. Bone grafting was deemed necessary in 17 patients. All patients have been followed for at least five years, and nine for up to 10 years. All patients were followed up with clinical and radiographic examinations, and in some cases rhinoscopy and sinoscopy as well. Three zygoma fixtures failed; two at the time of connection of the abutment and the third after six years. Of the conventional fixtures placed at the time of the zygoma fixture, 29 (27%) were lost. The overall prosthetic rehabilitation rate was 96% after at least five years of function. There were no signs of inflammatory reaction in the surrounding antral mucosa. Four patients with recurrent sinusitis recovered after inferior meatal antrostomy. To conclude, the zygoma fixture seems to be a valuable addition to our repertoire in the management of the compromised maxilla.

Bone Transplantation↗
PubMed2004

The Swedish National Programme for Quality Control of Secondary Prevention of Coronary Artery Disease--results after one year.

BACKGROUND: Guidelines for the prevention of coronary artery disease (CAD) have been developed both in Europe and in the USA. However, several surveys have shown that these guidelines are poorly implemented in clinical practice. DESIGN/METHODS: The Swedish Quality Control Programme on Secondary Prevention of CAD includes patients after myocardial infarction, or having undergone coronary artery surgery or percutaneous coronary intervention. Fifty of Sweden's 79 hospital districts are currently participating. Patients are asked to send report-cards regarding risk factor management to a central registry after discharge from hospital, at a 3-6 month visit and then yearly for 5 years. RESULTS: Results based on data from 1 year after the index event show that a majority of patients reach targets for serum cholesterol (70%), and low-density lipoprotein (LDL)-cholesterol (71%). Mean value for total cholesterol is 4.6 (+/-SD 0.9) mmol/l, LDL-cholesterol 2.7 (+/-SD 0.8) mmol/l. Blood pressure targets are less often achieved, with 58% reaching the European Society of Cardiology target for systolic (<140 mmHg) and 81% for diastolic (<90 mmHg) blood pressure. A large proportion of patients are prescribed preventive drugs: aspirin (96%), beta-blockers (78%) and lipid-lowering drugs (83%). CONCLUSIONS: The Swedish Quality Control Programme is one of the first attempts to assess implementation of guidelines on a national level based on patient participation. It is hoped that shared care programmes and increased patient involvement with feedback on achieved treatment goals in relation to guidelines will improve outcomes in patients with CAD.

Adrenergic beta-Antagonists↗
PubMed2004

Cambial meristem dormancy in trees involves extensive remodelling of the transcriptome.

The establishment of the dormant state in meristems involves considerable physiological and metabolic alterations necessary for surviving unfavourable growth conditions. However, a global molecular analysis of dormancy in meristems has been hampered by the difficulty in isolating meristem cells. We used cryosectioning to isolate purified cambial meristem cells from the woody plant Populus tremula during active growth and dormancy. These samples were used to generate meristem-specific cDNA libraries and for cDNA microarray experiments to define the global transcriptional changes underlying cambial dormancy. The results indicate a significant reduction in the complexity of the cambial transcriptome in the dormant state. Although cell division is terminated in the dormant cambium, the cell cycle machinery appears to be maintained in a skeletal state as suggested by the continued presence of transcripts for several cell cycle regulators. The downregulation of PttPIN1 and PttPIN2 transcripts explains the reduced basipetal polar auxin transport during dormancy. The induction of a member of the SINA family of ubiquitin ligases implicated in auxin signalling indicates a potential mechanism for modulation of auxin sensitivity during cambial dormancy. The metabolic alterations during dormancy are mirrored in the induction of genes involved in starch breakdown and the glyoxysomal cycle. Interestingly, the induction of RGA1 like gene suggests modification of gibberellin signalling in cambial dormancy. The induction of genes such as poplar orthologues of FIE and HAP2 indicates a potential role for these global regulators of transcription in orchestrating extensive changes in gene expression during dormancy.

Cell Cycle↗
PubMed2004

Forearm bone mineral density in 1294 middle-aged women: a strong predictor of fragility fractures.

The aim of this study was to find out whether a single bone mineral density (BMD) measurement performed at middle age in early postmenopausal women could predict future fragility fractures. The Malmo Preventive Project, a population-based cardiovascular prevention study, included a subgroup of 1294 women, mean age 53, on which forearm BMD measurements were made using single-photon absorptiometry (SPA). Risk ratios (RRs) were calculated for an age-adjusted decrease in BMD of one standard deviation. During the 9-yr follow-up, 65 women sustained 86 fractures. The data were analyzed with Cox's proportional hazard analysis. The relative risk for sustaining any fragility fracture were 2.02 (95% confidence interval [CI] = 1.56-2.61) and 1.62 (CI = 1.26-2.08) at the distal and proximal forearm BMD measurement, respectively. The risk increase was significant for forearm fracture at the distal BMD level (RR = 1.94; range = 1.40-2.68) and at the proximal BMD level (RR = 1.77; range = 1.29-2.42). Our study is one of the first to show that a BMD measurement in a population at age 50 can predict fracture over almost 10 yr, indicating that early identification of women with increased fracture risk is possible, and the cost-effectiveness of such an approach needs to be further evaluated.

Absorptiometry, Photon↗
PubMed2004

Amplification of mRNA populations by a cDNA tag strategy.

Here we describe an amplification method for global transcript analysis. The strategy relies on amplification of cDNA tags (signature tags) achieved by random fragmentation of the cDNAs to short tags of similar length, isolation of the 3' ends and then PCR amplification of the 3'-end signature tag population. This method minimizes biased amplification that may occur during parallel amplification of long and short templates. The amplified tags can be either cloned and sequenced or labeled and hybridized to DNA arrays to identify the expressed transcripts. To verify that the relative levels between transcripts in different mRNA/cDNA populations are maintained during the amplification protocol, we have used the Affymetrix oligonucleotide platform and real-time PCR.

DNA, Complementary↗
PubMed2004

DNA copy-number analysis of the 22q11 deletion-syndrome region using array-CGH with genomic and PCR-based targets.

Deletions and duplications of genomic segments commonly cause developmental disorders. The resolution and efficiency in diagnosing such gene-dosage alterations can be drastically increased using microarray-based comparative genomic hybridization (array-CGH). However, array-CGH currently relies on spotting genomic clones as targets, which confers severe limitations to the approach including resolution of analysis and reliable gene-dosage assessment of regions with high content of redundant sequences. To improve the methodology for analysis, we compared the use of genomic clones, repeat-free pools of amplified genomic DNA and cDNAs (single and pooled) as targets on the array. For this purpose, we chose q11.2 locus on chromosome 22 as a testing ground. Microdeletions at 22q11 cause birth defects collectively described as the DiGeorge/velocardiofacial syndrome. The majority of patients present 3 Mb typical deletions. Here, we report the construction of a gene-dosage array, covering 6 Mb of 22q11 and including the typically deleted region. We hybridized DNA from six DiGeorge syndrome patients to the array, and show that as little as 11.5 kb non-redundant, repeat-free PCR-generated sequence can be used for reliable detection of hemizygous deletions. By extrapolation, this would allow analysis of the genome with an average resolution of 25 kb. In the case of cDNAs our results indicate that 3.5 kb sequence is necessary for accurate identification of haploid/diploid dosage alterations. Thus, for regions rich in redundant sequences and repeats, such as 22q11, a specifically tailored array-CGH approach is good for gene copy number profiling.

Chromosomes, Human, Pair 22↗
PubMed2003

Minute quantities of misfolded mutant superoxide dismutase-1 cause amyotrophic lateral sclerosis.

Mutant forms of superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS) by an unknown noxious mechanism. Using an antibody against a novel epitope in the G127insTGGG mutation, mutant SOD1 was studied for the first time in spinal cord and brain of an ALS patient. The level was below 0.5% of the SOD1 level in controls. In corresponding transgenic mice the content of mutant SOD1 was also low, although it was enriched in spinal cord and brain compared with other tissues. In the mice the misfolded mutant SOD1 aggregated rapidly and 20% occurred in steady state as detergent-soluble protoaggregates. The misfolded SOD1 and the protoaggregates form, from birth until death, a potentially noxious burden that may induce the motor neuron injury. Detergent-resistant aggregates, as well as inclusions of mutant SOD1 in motor neurons and astrocytes, accumulated in spinal cord ventral horns of the patient and mice with terminal disease. The inclusions and aggregates may serve as terminal markers of long-term assault by misfolded SOD1 and protoaggregates.

Amyotrophic Lateral Sclerosis↗