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11.
Péterfy M Ben-Zeev O Mao HZ Weissglas-Volkov D Aouizerat BE Pullinger CR Frost PH Kane JP Malloy MJ Reue K Pajukanta P Doolittle MH 《Nature genetics》2007,39(12):1483-1487
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia. 相似文献
12.
Kertész A Váradi G Tóth GK Fajka-Boja R Monostori E Sármay G 《Cellular and molecular life sciences : CMLS》2006,63(22):2682-2693
Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We
showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated
binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target
cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into
B cells. We found octanoyl-Arg8 to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable
SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and
time-dependent manner.
Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006 相似文献
13.
Szade Agata Szade Krzysztof Mahdi Mahdi Józkowicz Alicja 《Cellular and molecular life sciences : CMLS》2021,78(10):4639-4651
Cellular and Molecular Life Sciences - Hematopoietic system transports all necessary nutrients to the whole organism and provides the immunological protection. Blood cells have high turnover,... 相似文献
14.
Most bony fishes rely on suction mechanisms to capture and transport prey. Once captured, prey are carried by water movement inside the oral cavity to a second set of jaws in the throat, the pharyngeal jaws, which manipulate the prey and assist in swallowing. Moray eels display much less effective suction-feeding abilities. Given this reduction in a feeding mechanism that is widespread and highly conserved in aquatic vertebrates, it is not known how moray eels swallow large fish and cephalopods. Here we show that the moray eel (Muraena retifera) overcomes reduced suction capacity by launching raptorial pharyngeal jaws out of its throat and into its oral cavity, where the jaws grasp the struggling prey animal and transport it back to the throat and into the oesophagus. This is the first described case of a vertebrate using a second set of jaws to both restrain and transport prey, and is the only alternative to the hydraulic prey transport reported in teleost fishes. The extreme mobility of the moray pharyngeal jaws is made possible by elongation of the muscles that control the jaws, coupled with reduction of adjacent gill-arch structures. The discovery that pharyngeal jaws can reach up from behind the skull to grasp prey in the oral jaws reveals a major innovation that may have contributed to the success of moray eels as apex predators hunting within the complex matrix of coral reefs. This alternative prey transport mode is mechanically similar to the ratcheting mechanisms used in snakes--a group of terrestrial vertebrates that share striking morphological, behavioural and ecological convergence with moray eels. 相似文献
15.
Cederwall B Moradi FG Bäck T Johnson A Blomqvist J Clément E de France G Wadsworth R Andgren K Lagergren K Dijon A Jaworski G Liotta R Qi C Nyakó BM Nyberg J Palacz M Al-Azri H Algora A de Angelis G Ataç A Bhattacharyya S Brock T Brown JR Davies P Di Nitto A Dombrádi Z Gadea A Gál J Hadinia B Johnston-Theasby F Joshi P Juhász K Julin R Jungclaus A Kalinka G Kara SO Khaplanov A Kownacki J La Rana G Lenzi SM Molnár J Moro R Napoli DR Singh BS Persson A Recchia F Sandzelius M Scheurer JN Sletten G 《Nature》2011,469(7328):68-71
Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis. 相似文献
16.
Timoney N Baumgart I Johanning M Varón AF Plenio MB Retzker A Wunderlich Ch 《Nature》2011,476(7359):185-188
Trapped atomic ions have been used successfully to demonstrate basic elements of universal quantum information processing. Nevertheless, scaling up such methods to achieve large-scale, universal quantum information processing (or more specialized quantum simulations) remains challenging. The use of easily controllable and stable microwave sources, rather than complex laser systems, could remove obstacles to scalability. However, the microwave approach has drawbacks: it involves the use of magnetic-field-sensitive states, which shorten coherence times considerably, and requires large, stable magnetic field gradients. Here we show how to overcome both problems by using stationary atomic quantum states as qubits that are induced by microwave fields (that is, by dressing magnetic-field-sensitive states with microwave fields). This permits fast quantum logic, even in the presence of a small (effective) Lamb-Dicke parameter (and, therefore, moderate magnetic field gradients). We experimentally demonstrate the basic building blocks of this scheme, showing that the dressed states are long lived and that coherence times are increased by more than two orders of magnitude relative to those of bare magnetic-field-sensitive states. This improves the prospects of microwave-driven ion trap quantum information processing, and offers a route to extending coherence times in all systems that suffer from magnetic noise, such as neutral atoms, nitrogen-vacancy centres, quantum dots or circuit quantum electrodynamic systems. 相似文献
17.
Voineagu I Wang X Johnston P Lowe JK Tian Y Horvath S Mill J Cantor RM Blencowe BJ Geschwind DH 《Nature》2011,474(7351):380-384
18.
19.
Determining the signalling pathways that direct tissue expansion is a principal goal of regenerative biology. Vigorous pancreatic β-cell replication in juvenile mice and humans declines with age, and elucidating the basis for this decay may reveal strategies for inducing β-cell expansion, a long-sought goal for diabetes therapy. Here we show that platelet-derived growth factor receptor (Pdgfr) signalling controls age-dependent β-cell proliferation in mouse and human pancreatic islets. With age, declining β-cell Pdgfr levels were accompanied by reductions in β-cell enhancer of zeste homologue 2 (Ezh2) levels and β-cell replication. Conditional inactivation of the Pdgfra gene in β-cells accelerated these changes, preventing mouse neonatal β-cell expansion and adult β-cell regeneration. Targeted human PDGFR-α activation in mouse β-cells stimulated Erk1/2 phosphorylation, leading to Ezh2-dependent expansion of adult β-cells. Adult human islets lack PDGF signalling competence, but exposure of juvenile human islets to PDGF-AA stimulated β-cell proliferation. The discovery of a conserved pathway controlling age-dependent β-cell proliferation indicates new strategies for β-cell expansion. 相似文献
20.