2006年结束，各大杂志会陆续邀请各方专家评出他们心目中的年度进展。今年第十二期的《Nature Medicine》已经评出他们的2006年十大医学进展，内容涉及到HIV的致病机制，老年痴呆的致病机制，p53的保护机制，肿瘤治疗，肥胖药物研究，造血干细胞的活动，抗抑郁药的作用，自身免疫相关的新细胞系，脑机接口技术，血管疾病的致病机制。CMBI还会收集其他相关杂志的评定结果，使大家可以对2006医学的发展有一个清晰、完整的映像。
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Nature Medicine年度十大医学进展
The tumor suppressor p53 was thought to protect from cancer by monitoring cells for DNA damage and eliminating potentially precancerous cells. But DNA damage may be irrelevant to p53’s protective effects, researchers reported in September. Instead a second tumor suppressor, p19ARF, may be the crucial signal for p53 to kill precancerous cells.
The pathological response to DNA damage does not contribute to p53-mediated tumour suppression (Nature 443, 214–217)
Three independent groups this year showed that HIV exhausts the ability of the immune system to combat infection by increasing the expression of a signaling molecule on CD8+ T cells and hampering their ability to respond to infected cells. The findings suggest a way to kick-start the immune system in HIV-infected individuals.
Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction (Nat. Med.12, 1198–1202)
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression (Nature 443, 350–354)
PD-1 is a regulator of virus-specifi c CD8+ T cell survival in HIV infection (J. Exp. Med. 203, 2281–2892)
The link between feeding and the brain’s sensing of nutrient levels was further cemented this year when scientists showed that injecting leucine into mouse brains activates mTOR, an enzyme known to regulate cell signaling and reduce eating. Rapamycin, an mTOR inhibitor, blocks this effect. The results suggest a possible target for obesity drugs.
Hypothalamic mTOR Signaling Regulates Food Intake (Science 312, 927–930)
Treating cancer by targeting the stem cells that give rise to tumors runs the risk of also killing normal stem cells, such as those that generate blood. Two groups this year identified key differences between normal and leukemia-initiating stem cells that might help target only cancer stem cells while sparing their normal counterparts.
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells (Nature 441, 475–483)
PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention (Nature 441, 518–522)
Three factors needed to drive hematopoietic stem cells from their niche in the bone marrow into the circulation were revealed this year. The stem cells’ mobilization requires sympathetic nervous system activity, a calcium-sensing receptor on their cell surface to tether the cells to the bone niche and the differentiation of osteoclasts, which releases enzymes to cleave tethering proteins.
Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone Marrow (Cell 124, 407–421)
Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor (Nature 439, 599–603)
Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells (Nat. Med. 12, 657–664)
Antidepressants may take several weeks to act, and their effects can extend for months after their use has been discontinued. How? Depression in mice induces remodeling of nuclear chromatin, altering gene expression, researchers reported in April. These epigenetic changes are reversed by antidepressants and may explain the drugs’ long-lasting effects.
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action (Nat. Neurosci. 9, 519–525)
A new class of CD4+ T cells, called TH17 cells, is thought to promote autoimmune disease. Two reports this year revealed that these cells are surprisingly closely linked to the protective regulatory T cells that dampen harmful immune responses: the cytokine TGF-β drives the development of both types.
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells (Nature 441, 235–238)
Transforming growth factor-β induces development of the TH17 lineage (Nature 441, 231–234)
Activity of the γ-secretase enzyme is crucial in Alzheimer disease. Researchers showed in September that presenilins, key components of the γ-secretase complex, form calcium channels in the endoplasmic reticulum. This channel function is independent of γ-secretase activity and is absent in mutant presenilins linked to genetic forms of Alzheimer disease, challenging the prevailing amyloid hypothesis.
Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer’s Disease-Linked Mutations (Cell 126, 981–993)
Two groups this year gave paralyzed individuals hope with remarkable advances in the area of brain-computer interfaces—or neuromotor prostheses. The interfaces enable a device implanted in the brain to translate electrical signals from neurons into external movement, allowing a tetraplegic man to move an electronic cursor as well as a robotic arm by thought. A second group increased the response speed of such interfaces.
A high-performance brain–computer interface (Nature 442, 164–171)
Neuronal ensemble control of prosthetic devices by a human with tetraplegia (Nature 442, 195–198)
Two studies this year showed how the activity of TGF-β cytokines contributes to vascular disease. The protein emilin prevents high blood pressure in mice caused by too much TGF-β activity. Higher levels of another antagonist, soluble endoglin, are present in pregnant women who develop pre-eclampsia— a major cause of maternal and fetal death— and trigger pre-eclamptic symptoms in mice.
Emilin1 Links TGF-β Maturation to Blood Pressure Homeostasis (Cell 124, 929–942)
Soluble endoglin contributes to the pathogenesis of preeclampsia (Nat. Med. 12, 642–649)
Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia (N. Engl. J. Med. 355, 992–1005) |
发表于 2007-4-6 12:53:39