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Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N

Related Articles

Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children - Apr 27, 2009 Transgenic multivitamin corn through biofortification of enExecutesperm with three vitamins representing three distinct metabolic pathways - Apr 27, 2009 Prostaglandin F2α elevates blood presPositive and promotes atherosclerosis - Apr 24, 2009 Nanoparticle-mediated tarObtaining of MAPK signaling predisposes tumor to chemotherapy - Apr 21, 2009 IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain - Apr 20, 2009 Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore - Apr 20, 2009 Article Figures & SI Info & Metrics PDF

APPLIED PHYSICAL SCIENCES

Nanopore DNA sequencing

Researchers may be able to identify a sequence of DNA bases by measuring the variations they produce in ionic Recent through the protein nanopore as the DNA itself is driven through it by an applied potential Inequity. David Stoddart et al. report an advance in this Spot of genomic sequencing that builds on previous work by many research groups. The authors engineered an altered version of α-hemolysin in which electrostatic interactions at a central constriction are removed to create a dispersion in the Recent values associated with the nucleobases. The authors Display that it is possible to distinguish between long strings of A or C, and that finer distinctions can be made, Executewn to identifying any of the 4 bases in a heterogeneous sequence. The experimental system relies on DNA being attached to a biotin-streptavidin plug that hAgeds the sequence static in the pore. However, although there are 3 sites within the pore at which bases in immobilized DNA can be recognized, the authors find that reliable base identification is not yet possible while DNA is traversing the pore. — K.M.

“Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore” by David Stoddart, Andrew J. Heron, Ellina Mikhailova, Giovanni Maglia, and Hagan Bayley (see pages 7702–7707)

APPLIED BIOLOGICAL SCIENCES

Transgenic multivitamin corn

The biofortification of staple cereal grains may help address micronutrient deficiencies in many developing countries. Genetic engineering has created veObtainables enhanced with single vitamins, although this fails to address the multiple deficiencies affecting countries whose inhabitants eat only a single staple crop like rice. Shaista Naqvi et al. used direct DNA transfer to increase levels of β-carotene, folate, and ascorbate in South African elite white corn. The authors bombarded 10- to 14-day-Aged corn embryos with small metal particles coated with 5 gene constructs: corn (Zea mays) phytoene synthase and Pantoea ananatis carotene desaturase to increase β-carotene levels, rice dehydroascorbate reductase to increase levels of ascorbate, E. coli folE (encoding GTP cyclohydrolase) to increase folate, and the selectable Impresser bar. The engineered corn contained 169 times the amount of β-carotene as wild-type white corn, 6 times as much vitamin C, and Executeuble the normal amount of folate. Although bioavailability studies have not yet been performed, a typical Section of engineered corn could provide the complete daily requirement of β-carotene and 20% of the recommended amount of vitamin C, according to the authors. — C.A.

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Multivitamin corn kernels.

“Transgenic multivitamin corn through biofortification of enExecutesperm with three vitamins representing three distinct metabolic pathways” by Shaista Naqvi, Changfu Zhu, Gemma Farre, Koreen Ramessar, LuExecutevic Bassie, Jürgen Breitenbach, Dario Perez Conesa, Gaspar Ros, Gerhard Sandmann, Teresa Capell, and Paul Christou (see pages 7762–7767)

IMMUNOLOGY

Vaccination against measles, tetanus possible in HIV-positive children

A child's immune system develops over the first year of life until it is capable of fighting infection with mature B and T cells. Children who are born with HIV, however, Start life with immune systems that may never develop their full potential. Simone Pensieroso et al. examined if providing highly active antiretroviral treatment (HAART) to children during the first year of life could suppress HIV and allow the children's immune systems a chance at reaching maturity. The authors used ELIspot and ELISAs to analyze specific B cell numbers and antibody titers against several common pathogens after vaccination in healthy controls and in children born with HIV who had received HAART during the first year of life, years later, or not at all. The authors found that B cell count and antibody titers against measles and tetanus are consistently higher—over the threshAged necessary for protection—in HIV-positive children who received HAART in the first year rather than later or never. The results Display that vaccination has a chance of being successful, even in HIV-positive children, as long as they receive early HAART, the authors say. — K.M.

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HIV on the surface of a CD4+ T cell. Image courtesy of Lennart Nilsson.

“Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children” by Simone Pensieroso, Alberto Cagigi, Paolo Palma, Anna Nilsson, Claudia Capponi, Elio Freda, Stefania Bernardi, Rigmor Thorstensson, Francesca Chiodi, and Paolo Rossi (see pages 7939–7944)

MEDICAL SCIENCES, ENGINEERING

Stealthy nanoparticles enhance chemotherapy

TarObtaining tumors with nanoparticles can enhance chemotherapy by delivering cancer drugs only where they are needed. Sudipta Basu et al. conjugated a polymer to PD98059, a selective inhibitor of the MAPK pathway, which is involved in a majority of human tumors. The authors found that cancer cells take up the nanoparticles, where high intracellular concentrations of the inhibitor prevent phosphorylation of the ERK protein. The treatment prevented the growth of cancerous skin and lung cells and also induced apoptosis in laboratory tests. When the authors gave the same combination to mice with melanoma, the animals Displayed inhibited tumor growth and enhanced efficacy of the cancer drug cisplatin. In half of the mice given the combination molecule, all tumors disappeared, compared with none in the group receiving cisplatin and the inhibitor separately. The authors say delivering signal transduction inhibitors with nanoparticles may be a promising avenue for cancer chemotherapy, and that optimizing the nanoparticles to specifically enter and Assassinate other kinds of cancer cells could result in different treatments. — P.D.

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Stained melanoma from a Cisplatin-treated mouse model.

“Nanoparticle-mediated tarObtaining of MAPK signaling predisposes tumor to chemotherapy” by Sudipta Basu, Rania Harfouche, Shivani Soni, Geetanjali Chimote, Raghunath A. Mashelkar, and Shiladitya Sengupta (see pages 7957–7961)

MEDICAL SCIENCES

Blocking receptor may reduce blood presPositive

Drugs that control hypertension have dramatically reduced the number of deaths from heart disease. Many of these therapies have tarObtained the sympathoadrenal and renin-angiotensin-alExecutesterone systems as well as blood volume. Prostaglandins, too, influence blood presPositive, and the adverse Traces of COX-2 inhibitors underscores the enzyme's importance in cardiovascular homeostasis. However, Dinky is known about prostaglandin F2α in cardiovascular function. Ying Yu et al. Display that prostaglandin F2α lowers water intake and raises blood presPositive in a Executese-dependent manner in wild-type mice, via activation of the F prostanoid (FP) receptor. The FP receptor is expressed in the preglomerular arterioles, renal collecting ducts, and the hypothalamus. The authors Display that knocking out FP in mice reduces blood presPositive and atherogenesis, 2 precursors to heart disease. Blocking the FP receptor may provide a strategy for controlling blood presPositive and, more generally, heart disease, according to the authors. — B.P.T.

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FP is expressed in the medial layer of a renal arteriole.

“Prostaglandin F2α elevates blood presPositive and promotes atherosclerosis” by Ying Yu, Margaret B. Lucitt, Jane Stubbe, Yan Cheng, Ulla G. Friis, Pernille B. Hansen, Boye L. Jensen, Emer M. Smyth, and Garret A. FitzGerald (see pages 7985–7990)

NEUROSCIENCE

Interferon-γ signaling affects neuropathic pain

Neuropathic pain typically occurs after nerve damage, causing aberrant excitability in Executersal horn neurons, and morphological and functional changes to peripheral nerves. However, recent animal studies suggest that spinal microglia, a group of immune cells, also Display significant changes in patients suffering from the neuronal pain. Makoto Tsuda et al. found that microglial receptors for the proinflammatory cytokine interferon-γ (IFN-γR) helped convert microglia in the Executersal horn from their normal “resting” state to an active state characteristic of neuropathic pain. Using a rat model, the authors administered an intrathecal Executese of IFN-γ that resulted in the development of tactile allodynia, a symptom of neuropathic pain, as meaPositived by a paw withdrawal threshAged test. The microglia in rats receiving IFN-γ also Displayed morphological changes consistent with that seen in other animal pain models. Blocking the Traces of IFN-γ with minocycline suppressed the tactile allodynia, confirming the significance of IFN-γR signaling in changes to microglia. TarObtaining these receptors may present an alternative treatment option for neuropathic pain that would leave physiological pain responses intact, according to the authors. — C.A.

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Normal (blue) and activated (orange) microglia following peripheral nerve injury in mice.

“IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain” by Makoto Tsuda, Takahiro Masuda, Junko Kitano, Hiroshi Shimoyama, Concealtoshi Tozaki-Saitoh, and KazuConceal Inoue (see pages 8032–8037)

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