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Papers recently published online by Nature and the Nature Research Journals
July 15, 2003NATURE MEDICINE(http://www.nature.com/naturemedicine)
[1] Cadmium's disguise does damage to estrogen-sensitive tissues
DOI: 10.1038/nm902 (http://dx.doi.org/10.1038/nm902)
With 15,000 tons produced each year for batteries, alloys, and pigments, the heavy metal cadmium is one of the most serious environmental pollutants. Chronic exposure can induce kidney damage and bone disease and is thought to cause cancer. A study in the August issue of Nature Medicine now shows that cadmium mimics the effects of estrogen, and suggests that even at relatively low doses cadmium might have wide-ranging effects on the body.
Mary Beth Martin and colleagues report that, in rats, cadmium induces several well-known estrogenic responses. These included increased uterine weight, changes in the endometrial lining and increased density of the epithelia of the mammary gland. Moreover, in utero exposure to cadmium affected mammary gland development and onset of puberty in female offspring. The results provide solid evidence that cadmium has estrogenic effects in the whole animal, and follow up on earlier studies reporting that cadmium and other heavy metals such as nickel interact with the estrogen receptor. The new data also broaden the toxic repertoire of cadmium, which is a known kidney toxin, and was recently shown (Jin et al., Nat. Genet. 34, 326-329; 2003) to impair DNA repair processes in yeast.
The investigators did not perform dose-response studies but they found that cadmium induced potent estrogenic responses in rats at doses (5-10 micrograms per kilogram total weight) comparable to the Provisional Tolerable Weekly Intake recommended by the World Health Organization (7 micrograms per kilogram per week). In addition to pinpointing another mechanism for some of cadmium's effects, the new data could call into question current regulatory standards for cadmium exposure.
Author contact:
Mary Beth Martin (Georgetown University, Washington, DC, USA)
Tel: +1 202 687 3768; E-mail: martinmb@georgetown.edu
[2] Battling the brainstorm
DOI: 10.1038/nm901 (http://dx.doi.org/10.1038/nm901)
Even with optimal drug therapy, more than 30% of patients with epilepsy continue to have seizures. A study in the August issue of Nature Medicine offers hope that some of these patients might someday respond to therapies designed to produce seizure-repressing compounds directly in the brain.
Thomas McCown and colleagues used a gene therapy approach to successfully overproduce one such anticonvulsant compound, galanin, in the rat brain. Galanin is a peptide that is normally widely distributed in the brain-the investigators simply boosted its production in certain nerve cells. This treatment was able to prevent seizures in a model similar to focal epilepsy, which originates in one part of the brain and then spreads. Most patients with epilepsy suffer from focal seizures. The investigators also tested the treatment in a model of statis epilepticus, a seizure that lasts 30 minutes or more and often results in brain damage. Although the treatment did not prevent seizures, it did reduce the brain damage that accompanies them.
Author contact:
Thomas McCown (University of North Carolina School of Medicine, Chapel Hill, NC, USA)
Tel: +1 919 966 3081; E-mail: thomas_mccown@med.unc.edu
Other papers from Nature Medicine to be published online at the same time and with the same embargo:
[3] Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma (DOI: 10.1038/nm903) (http://dx.doi.org/10.1038/nm903)
[4] Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A (DOI: 10.1038/nm899) (http://dx.doi.org/10.1038/nm899)
***************************************
Items from other Nature journals to be published online at the same time and with the same embargo:
NATURE (http://www.nature.com/nature)
[5] Crystal structure of human cytochrome P450 2C9 with bound warfarin (DOI: 10.1038/nature01862) (http://dx.doi.org/10.1038/nature01862)
NATURE MATERIALS (http://www.nature.com/naturematerials)
[6] Fabrication of solid-state nanopores with single-nanometre precision (DOI: 10.1038/nmat941) (http://dx.doi.org/10.1038/nmat941)
[7] Identification of ultradilute dopants in ceramics (DOI: 10.1038/nmat939) (http://dx.doi.org/10.1038/nmat939)
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
[8] Metabolic labeling of C. elegans and D. melanogaster for quantitative proteomics (DOI: 10.1038/nbt848) (http://dx.doi.org/10.1038/nbt848) (http://dx.doi.org/10.1038/nbt848)
[9] Genetic manipulation of gibberellin metabolism in transgenic rice (DOI: 10.1038/nbt847) (http://dx.doi.org/10.1038/nbt847)
[10] Targeting of proteins to membranes through hedgehog auto-processing (DOI: 10.1038/nbt844) (http://dx.doi.org/10.1038/nbt844)
NATURE GENETICS (http://www.nature.com/naturegenetics)
[11] Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools (DOI: 10.1038/ng1212) (http://dx.doi.org/10.1038/ng1212)
[12] Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS) (DOI: 10.1038/ng1213) (http://dx.doi.org/10.1038/ng1213)
[13] Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency (DOI: 10.1038/ng1214) (http://dx.doi.org/10.1038/ng1214)
NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[14] Localization of PIP2 activation gate in inward rectifier K+ channels (DOI: 10.1038/nn1090) (http://dx.doi.org/10.1038/nn1090)
[15] TRPC5 is a regulator of hippocampal neurite length and growth cone morphology (DOI: 10.1038/nn1092) (http://dx.doi.org/10.1038/nn1092)
[16] Modulation of glycine-activated ion channel function by G-protein betagamma subunits (DOI: 10.1038/nn1095) (http://dx.doi.org/10.1038/nn1095)
[17] Microstimulation of visual cortex affects the speed of perceptual decisions (DOI: 10.1038/nn1094) (http://dx.doi.org/10.1038/nn1094)
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
[18] Continuous T cell receptor signaling required for synapse maintenance and full effector potential (DOI: 10.1038/ni951) (http://dx.doi.org/10.1038/ni951)
[19] Genetically linked C-type lectin-related ligands for NKRP1 family of natural killer cell receptors (DOI: 10.1038/ni954) (http://dx.doi.org/10.1038/ni954)
[20] The influence of the thymic environment on the CD4-versus-CD8 T lineage decision (DOI: 10.1038/ni953) (http://dx.doi.org/10.1038/ni953)
NATURE STRUCTURAL BIOLOGY (http://www.nature.com/naturestructuralbiology)
[21] The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators (DOI: 10.1038/nsb956) (http://dx.doi.org/10.1038/nsb956)
[22] Structural basis for binding of accessory proteins by the appendage domain of GGAs (DOI: 10.1038/nsb955) (http://dx.doi.org/10.1038/nsb955)
[23] Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3 (DOI: 10.1038/nsb953) (http://dx.doi.org/10.1038/nsb953)
Nature Publishing Group Reference
With 15,000 tons produced each year for batteries, alloys, and pigments, the heavy metal cadmium is one of the most serious environmental pollutants. Chronic exposure can induce kidney damage and bone disease and is thought to cause cancer. A study in the August issue of Nature Medicine now shows that cadmium mimics the effects of estrogen, and suggests that even at relatively low doses cadmium might have wide-ranging effects on the body.
Mary Beth Martin and colleagues report that, in rats, cadmium induces several well-known estrogenic responses. These included increased uterine weight, changes in the endometrial lining and increased density of the epithelia of the mammary gland. Moreover, in utero exposure to cadmium affected mammary gland development and onset of puberty in female offspring. The results provide solid evidence that cadmium has estrogenic effects in the whole animal, and follow up on earlier studies reporting that cadmium and other heavy metals such as nickel interact with the estrogen receptor. The new data also broaden the toxic repertoire of cadmium, which is a known kidney toxin, and was recently shown (Jin et al., Nat. Genet. 34, 326-329; 2003) to impair DNA repair processes in yeast.
The investigators did not perform dose-response studies but they found that cadmium induced potent estrogenic responses in rats at doses (5-10 micrograms per kilogram total weight) comparable to the Provisional Tolerable Weekly Intake recommended by the World Health Organization (7 micrograms per kilogram per week). In addition to pinpointing another mechanism for some of cadmium's effects, the new data could call into question current regulatory standards for cadmium exposure.
Author contact:
Mary Beth Martin (Georgetown University, Washington, DC, USA)
Tel: +1 202 687 3768; E-mail: martinmb@georgetown.edu
[2] Battling the brainstorm
DOI: 10.1038/nm901 (http://dx.doi.org/10.1038/nm901)
Even with optimal drug therapy, more than 30% of patients with epilepsy continue to have seizures. A study in the August issue of Nature Medicine offers hope that some of these patients might someday respond to therapies designed to produce seizure-repressing compounds directly in the brain.
Thomas McCown and colleagues used a gene therapy approach to successfully overproduce one such anticonvulsant compound, galanin, in the rat brain. Galanin is a peptide that is normally widely distributed in the brain-the investigators simply boosted its production in certain nerve cells. This treatment was able to prevent seizures in a model similar to focal epilepsy, which originates in one part of the brain and then spreads. Most patients with epilepsy suffer from focal seizures. The investigators also tested the treatment in a model of statis epilepticus, a seizure that lasts 30 minutes or more and often results in brain damage. Although the treatment did not prevent seizures, it did reduce the brain damage that accompanies them.
Author contact:
Thomas McCown (University of North Carolina School of Medicine, Chapel Hill, NC, USA)
Tel: +1 919 966 3081; E-mail: thomas_mccown@med.unc.edu
Other papers from Nature Medicine to be published online at the same time and with the same embargo:
[3] Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma (DOI: 10.1038/nm903) (http://dx.doi.org/10.1038/nm903)
[4] Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A (DOI: 10.1038/nm899) (http://dx.doi.org/10.1038/nm899)
***************************************
Items from other Nature journals to be published online at the same time and with the same embargo:
NATURE (http://www.nature.com/nature)
[5] Crystal structure of human cytochrome P450 2C9 with bound warfarin (DOI: 10.1038/nature01862) (http://dx.doi.org/10.1038/nature01862)
NATURE MATERIALS (http://www.nature.com/naturematerials)
[6] Fabrication of solid-state nanopores with single-nanometre precision (DOI: 10.1038/nmat941) (http://dx.doi.org/10.1038/nmat941)
[7] Identification of ultradilute dopants in ceramics (DOI: 10.1038/nmat939) (http://dx.doi.org/10.1038/nmat939)
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
[8] Metabolic labeling of C. elegans and D. melanogaster for quantitative proteomics (DOI: 10.1038/nbt848) (http://dx.doi.org/10.1038/nbt848) (http://dx.doi.org/10.1038/nbt848)
[9] Genetic manipulation of gibberellin metabolism in transgenic rice (DOI: 10.1038/nbt847) (http://dx.doi.org/10.1038/nbt847)
[10] Targeting of proteins to membranes through hedgehog auto-processing (DOI: 10.1038/nbt844) (http://dx.doi.org/10.1038/nbt844)
NATURE GENETICS (http://www.nature.com/naturegenetics)
[11] Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools (DOI: 10.1038/ng1212) (http://dx.doi.org/10.1038/ng1212)
[12] Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS) (DOI: 10.1038/ng1213) (http://dx.doi.org/10.1038/ng1213)
[13] Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency (DOI: 10.1038/ng1214) (http://dx.doi.org/10.1038/ng1214)
NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[14] Localization of PIP2 activation gate in inward rectifier K+ channels (DOI: 10.1038/nn1090) (http://dx.doi.org/10.1038/nn1090)
[15] TRPC5 is a regulator of hippocampal neurite length and growth cone morphology (DOI: 10.1038/nn1092) (http://dx.doi.org/10.1038/nn1092)
[16] Modulation of glycine-activated ion channel function by G-protein betagamma subunits (DOI: 10.1038/nn1095) (http://dx.doi.org/10.1038/nn1095)
[17] Microstimulation of visual cortex affects the speed of perceptual decisions (DOI: 10.1038/nn1094) (http://dx.doi.org/10.1038/nn1094)
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
[18] Continuous T cell receptor signaling required for synapse maintenance and full effector potential (DOI: 10.1038/ni951) (http://dx.doi.org/10.1038/ni951)
[19] Genetically linked C-type lectin-related ligands for NKRP1 family of natural killer cell receptors (DOI: 10.1038/ni954) (http://dx.doi.org/10.1038/ni954)
[20] The influence of the thymic environment on the CD4-versus-CD8 T lineage decision (DOI: 10.1038/ni953) (http://dx.doi.org/10.1038/ni953)
NATURE STRUCTURAL BIOLOGY (http://www.nature.com/naturestructuralbiology)
[21] The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators (DOI: 10.1038/nsb956) (http://dx.doi.org/10.1038/nsb956)
[22] Structural basis for binding of accessory proteins by the appendage domain of GGAs (DOI: 10.1038/nsb955) (http://dx.doi.org/10.1038/nsb955)
[23] Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3 (DOI: 10.1038/nsb953) (http://dx.doi.org/10.1038/nsb953)
Nature Publishing Group Reference
Seizures Current Events and Seizures News RSSResearchers begin to decipher metabolism of sexual assault drug
It's a naturally occurring brain chemical with an unwieldy name: 4-hydroxybutyrate (4-HB). Taken by mouth, it can be abused or used as a date-rape drug.
Greater certainty in monitoring 3 therapeutic medications is facilitated by new CRMs
To help bring greater certainty to the measurement of medication levels in a patient's bloodstream for three drugs with narrow therapeutic ranges, the U.S. Pharmacopeial Convention (USP) is releasing new certified reference materials (CRMs).
Research reveals lipids' unexpected role in triggering death of brain cells
The lipid that accumulates in brain cells of individuals with an inherited enzyme disorder also drives the cell death that is a hallmark of the disease, according to new research led by St. Jude Children's Research Hospital investigators.
Protein critical for insulin secretion may be contributor to diabetes
A cellular protein from a family involved in several human diseases is crucial for the proper production and release of insulin, new research has found, suggesting that the protein might play a role in diabetes.
A new understanding of why seizures occur with alcohol withdrawal
Epileptic seizures are the most dramatic and prominent aspect of the "alcohol withdrawal syndrome" that occurs when a person abruptly stops a long-term or chronic drinking habit. Researchers have shown that the flow of calcium ions into brain cells via voltage-gated calcium channels plays an important role in the generation of alcohol withdrawal seizures, because blocking this flow suppresses these seizures.
Packages of care for epilepsy in low- and middle-income countries
In the second in a six part series on treating mental health problems in resource-poor settings, Caroline Mbuba and Charles Newton (Centre for Geographic Medicine Research, Kenya Medical Research Institute, Kilifi, Kenya) discuss "packages of care" for treating epilepsy.
Study pinpoints key mechanism in brain development, raising question about use of antiseizure drug
Researchers at the Stanford University School of Medicine have identified a key molecular player in guiding the formation of synapses - the all-important connections between nerve cells - in the brain.
Research ensures 50 million vaccinated against deadly brain infection
Research at the University of Liverpool has supported the vaccination of more than 50 million people against a zoonotic brain infection that affects thousands of children across Asia every year.
Universal screening lowers risk of severe jaundice in infants
Screening all newborns for excessive bilirubin in the blood can significantly decrease the incidence of severe jaundice which, in extreme cases, can lead to seizures and brain damage.
High-res view of zinc transport protein
How much difference can a tenth of a nanometer make? When it comes to figuring out how proteins work, an improvement in resolution of that miniscule amount can mean the difference between seeing where atoms are and understanding how they interact.
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