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Nature and the Nature research journals press release
March 22, 2005[1] Predicting stroke risk in sickle cell anemia
DOI: 10.1038/ng1533
A new study published in the April issue of Nature Genetics provides a predictive model that can identify sickle cell anemia (SCA) patients at risk of stroke with greater accuracy and faster than current methods allow, which may be useful as a prognostic test. Stroke is a major risk factor for sickle cell anemia patients under 20 years of age.
Paola Sebastiani, Marco Ramoni and colleagues analyzed 235 variations in 80 candidate genes in 1,398 sickle cell anemia patients, in order to develop a model that captured the genetic and clinical factors that influenced the risk of stroke. The authors validated the model in an independent population of 114 subjects, correctly predicting the occurrence of stroke with 98.2% accuracy. The analysis found that 25 variations within 11 genes, combined with 4 clinical variables, interact to significantly influence the risk of stroke. These include some factors previously associated with stroke in the general population, including 3 genes in the TGF-beta pathway as well as hemoglobin levels. This provides evidence that stroke risk is a complex trait with multiple genetic and clinical influences, and suggests candidates that may be important in predicting stroke risk in the general population.
Currently, Transcranial Doppler (TCD) flow studies are used to predict the likelihood of stroke in children and young adults with SCA. However, the usefulness of this as a predictive test is limited, as only 10% of cases with abnormal TCD values will have a stroke, while some individuals with normal values will have a stroke.
Author Contact:
Marco Ramoni
(Harvard Medical School, Boston, MA, USA)
Tel: +1 617 525 4466, Cell: +1 617 823 7468, Email: marco_ramoni@harvard.edu
Paola Sebastiani
(Boston University School of Public Health, Boston, MA, USA)
Tel: +1 617 638 5877, Email: sebas@bu.edu
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
[2] Reverse engineering of regulatory networks in human B cells
DOI: 10.1038/ng1532
[3] An empirical test of the mutational landscape model of adaptation using a single-stranded DNA virus
DOI: 10.1038/ng1535
*****
NATURE CELL BIOLOGY
(http://www.nature.com/naturecellbiology)
[4] Wnt signals two ways to a healthy gut
DOI: 10.1038/ncb1240
The same signal that ensures that there are cells available to keep your intestine replenished also controls a cell type that is required to defend against bacterial infection, according to a study published online this week in Nature Cell Biology.
The Wnt signalling system is known to control the turnover of cells in the gut, and over-activation of this system leads to intestinal tumours. The new findings from Dr. Hans Clevers and colleagues bring a note of caution for cancer therapies aimed at blocking Wnt signalling because this could also adversely affect the availability of these bacterial defence cells.
Wnt signals are known to be necessary for maintaining a pool of undifferentiated intestinal progenitor cells, which can replenish all the different cell types of the intestine in response to injury among other things. This new study shows that Wnt signals also control both the maturation and the correct positioning of a specific type of intestine cell -- the Paneth cell --which is known to be important for secreting anti-bacterial peptides.
This dual role of Wnt -- maintaining a progenitor cell while also inducing a mature cell -- is demonstrated by the observation that intestinal tumour cells, resulting from overproduction of the progenitor cells, also show some molecular characteristics of mature Paneth cells.
Author contact:
Dr. Hans Clevers
(Netherlands Institute for Developmental Biology, Utrecht, The Netherlands)
Tel: +31 302121826, Email: clevers@niob.knaw.nl
*****
Nature journals to be published online at the same time and with the same embargo:
NATURE MATERIALS (http://www.nature.com/naturematerials)
[5] Trans-interface diffusion-controlled coarsening
DOI: 10.1038/nmat1340
[6] Spin-conserving carrier recombination in conjugated polymers
DOI: 10.1354/nmat1354
[7] Duality of fatigue failures of materials caused by Poisson defect statistics of competing failure modes
DOI: 10.1051/nmat1351
[8] Quantum criticality and universal scaling of a quantum antiferromagnet
DOI: 10.1327/nmat1327
NATURE MEDICINE (http://www.nature.com/naturemedicine)
[9] A new transgene reporter for in vivo magnetic resonance imaging
DOI: 10.1038/nm1208
[10] Somatostatin regulates brain amyloid beta peptide Abeta 42 through modulation of proteolytic degradation
DOI: 10.1038/nm1206
[11] Angiopoietin-related growth factor antagonizes obesity and insulin resistance
DOI: 10.1038/nm1214
NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[12] AlphaCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory
DOI: 10.1038/nn1431
[13] G protein beta-gamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis
DOI: 10.1038/nn1423
[14] Protocadherin Celsr3 is crucial in axonal tract development
DOI: 10.1038/nn1428
[15] Virtual lesions of the anterior intraparietal area disrupt goal-dependent on-line adjustments of grasp
DOI: 10.1038/nn1430
NATURE STRUCTURAL AND MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[16] The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle
DOI: 10.1038/nsmb914
[17] Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase C
DOI: 10.1038/nsmb915
Nature Publishing Group Reference
Paola Sebastiani, Marco Ramoni and colleagues analyzed 235 variations in 80 candidate genes in 1,398 sickle cell anemia patients, in order to develop a model that captured the genetic and clinical factors that influenced the risk of stroke. The authors validated the model in an independent population of 114 subjects, correctly predicting the occurrence of stroke with 98.2% accuracy. The analysis found that 25 variations within 11 genes, combined with 4 clinical variables, interact to significantly influence the risk of stroke. These include some factors previously associated with stroke in the general population, including 3 genes in the TGF-beta pathway as well as hemoglobin levels. This provides evidence that stroke risk is a complex trait with multiple genetic and clinical influences, and suggests candidates that may be important in predicting stroke risk in the general population.
Currently, Transcranial Doppler (TCD) flow studies are used to predict the likelihood of stroke in children and young adults with SCA. However, the usefulness of this as a predictive test is limited, as only 10% of cases with abnormal TCD values will have a stroke, while some individuals with normal values will have a stroke.
Author Contact:
Marco Ramoni
(Harvard Medical School, Boston, MA, USA)
Tel: +1 617 525 4466, Cell: +1 617 823 7468, Email: marco_ramoni@harvard.edu
Paola Sebastiani
(Boston University School of Public Health, Boston, MA, USA)
Tel: +1 617 638 5877, Email: sebas@bu.edu
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
[2] Reverse engineering of regulatory networks in human B cells
DOI: 10.1038/ng1532
[3] An empirical test of the mutational landscape model of adaptation using a single-stranded DNA virus
DOI: 10.1038/ng1535
*****
NATURE CELL BIOLOGY
(http://www.nature.com/naturecellbiology)
[4] Wnt signals two ways to a healthy gut
DOI: 10.1038/ncb1240
The same signal that ensures that there are cells available to keep your intestine replenished also controls a cell type that is required to defend against bacterial infection, according to a study published online this week in Nature Cell Biology.
The Wnt signalling system is known to control the turnover of cells in the gut, and over-activation of this system leads to intestinal tumours. The new findings from Dr. Hans Clevers and colleagues bring a note of caution for cancer therapies aimed at blocking Wnt signalling because this could also adversely affect the availability of these bacterial defence cells.
Wnt signals are known to be necessary for maintaining a pool of undifferentiated intestinal progenitor cells, which can replenish all the different cell types of the intestine in response to injury among other things. This new study shows that Wnt signals also control both the maturation and the correct positioning of a specific type of intestine cell -- the Paneth cell --which is known to be important for secreting anti-bacterial peptides.
This dual role of Wnt -- maintaining a progenitor cell while also inducing a mature cell -- is demonstrated by the observation that intestinal tumour cells, resulting from overproduction of the progenitor cells, also show some molecular characteristics of mature Paneth cells.
Author contact:
Dr. Hans Clevers
(Netherlands Institute for Developmental Biology, Utrecht, The Netherlands)
Tel: +31 302121826, Email: clevers@niob.knaw.nl
*****
Nature journals to be published online at the same time and with the same embargo:
NATURE MATERIALS (http://www.nature.com/naturematerials)
[5] Trans-interface diffusion-controlled coarsening
DOI: 10.1038/nmat1340
[6] Spin-conserving carrier recombination in conjugated polymers
DOI: 10.1354/nmat1354
[7] Duality of fatigue failures of materials caused by Poisson defect statistics of competing failure modes
DOI: 10.1051/nmat1351
[8] Quantum criticality and universal scaling of a quantum antiferromagnet
DOI: 10.1327/nmat1327
NATURE MEDICINE (http://www.nature.com/naturemedicine)
[9] A new transgene reporter for in vivo magnetic resonance imaging
DOI: 10.1038/nm1208
[10] Somatostatin regulates brain amyloid beta peptide Abeta 42 through modulation of proteolytic degradation
DOI: 10.1038/nm1206
[11] Angiopoietin-related growth factor antagonizes obesity and insulin resistance
DOI: 10.1038/nm1214
NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[12] AlphaCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory
DOI: 10.1038/nn1431
[13] G protein beta-gamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis
DOI: 10.1038/nn1423
[14] Protocadherin Celsr3 is crucial in axonal tract development
DOI: 10.1038/nn1428
[15] Virtual lesions of the anterior intraparietal area disrupt goal-dependent on-line adjustments of grasp
DOI: 10.1038/nn1430
NATURE STRUCTURAL AND MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[16] The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle
DOI: 10.1038/nsmb914
[17] Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase C
DOI: 10.1038/nsmb915
Nature Publishing Group Reference
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Fat around the middle increases the risk of dementia
Women who store fat on their waist in middle age are more than twice as likely to develop dementia when they get older, reveals a new study from the Sahlgrenska Academy.
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Multiple health concerns surface as winter, vitamin D deficiences arrive
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New understanding about mechanism for cell death after stroke leads to possible therapy
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Night Beat, Overtime and a Disrupted Sleep Pattern Can Harm Officers' Health
A police officer who works the night shift, typically from 8 p.m. to 4 a.m., already is at a disadvantage when it comes to getting a good "night's" sleep.
Vitamin B niacin offers no extra benefit to statin therapy in seniors already diagnosed with CAD
The routine prescription of extended-release niacin, a B vitamin (1,500 milligrams daily), in combination with traditional cholesterol-lowering therapy offers no extra benefit in correcting arterial narrowing and diminishing plaque buildup in seniors who already have coronary artery disease, a new vascular imaging study from Johns Hopkins experts shows.
The benefits of exercise
Physical exercise is one of the most effective methods of preventing disease. The current issue of Deutsches Arzteblatt International is devoted to this important topic.
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