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Liou YC  Sun A  Ryo A  Zhou XZ  Yu ZX  Huang HK  Uchida T  Bronson R  Bing G  Li X  Hunter T  Lu KP 《Nature》2003,424(6948):556-561
The neuropathological hallmarks of Alzheimer's disease and other tauopathies include senile plaques and/or neurofibrillary tangles. Although mouse models have been created by overexpressing specific proteins including beta-amyloid precursor protein, presenilin and tau, no model has been generated by gene knockout. Phosphorylation of tau and other proteins on serine or threonine residues preceding proline seems to precede tangle formation and neurodegeneration in Alzheimer's disease. Notably, these phospho(Ser/Thr)-Pro motifs exist in two distinct conformations, whose conversion in some proteins is catalysed by the Pin1 prolyl isomerase. Pin1 activity can directly restore the conformation and function of phosphorylated tau or it can do so indirectly by promoting its dephosphorylation, which suggests that Pin1 is involved in neurodegeneration; however, genetic evidence is lacking. Here we show that Pin1 expression is inversely correlated with predicted neuronal vulnerability and actual neurofibrillary degeneration in Alzheimer's disease. Pin1 knockout in mice causes progressive age-dependent neuropathy characterized by motor and behavioural deficits, tau hyperphosphorylation, tau filament formation and neuronal degeneration. Thus, Pin1 is pivotal in protecting against age-dependent neurodegeneration, providing insight into the pathogenesis and treatment of Alzheimer's disease and other tauopathies.  相似文献   
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Western juniper ( Juniperus occidentalis spp. occidentalis ) has rapidly expanded into shrub steppe communities in the intermountain Northwest during the past 120 yr. Cutting juniper is a management tool used to restore shrub steppe communities. Response of the understory after cutting is strongly influenced by plant species composition existing prior to treatment. This study assessed distribution patterns of understory plants over 2 growing seasons after tree cutting in a western juniper woodland. Cover, density, and diversity of understory species were compared among 3 locations: interspaces, duff zones (previously under tree canopies), and debris zones (beneath cut trees). Plant cover density increased in all zones following tree cutting. Understory vegetation in cut woodlands exhibited strong zonal distribution. Cover and density of Poa sandbergii and Sitanion hystrix and canopy cover of annual forbs were greatest in duff zones ( P P < 0.05). Debris zones tended to have the lowest overall understory cover and plant density values. Under juniper debris many species common to interspaces were reduced in density, although plants that survived or established beneath debris grew larger than their counterparts in interspaces. Species increased in density and cover under debris were plants characteristic of duff zones and whose seeds are typically wind dispersed.  相似文献   
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Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced gut–brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal lipid-induced gut–brain–liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids.  相似文献   
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Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.  相似文献   
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Towards sustainability in world fisheries   总被引:70,自引:0,他引:70  
Fisheries have rarely been 'sustainable'. Rather, fishing has induced serial depletions, long masked by improved technology, geographic expansion and exploitation of previously spurned species lower in the food web. With global catches declining since the late 1980s, continuation of present trends will lead to supply shortfall, for which aquaculture cannot be expected to compensate, and may well exacerbate. Reducing fishing capacity to appropriate levels will require strong reductions of subsidies. Zoning the oceans into unfished marine reserves and areas with limited levels of fishing effort would allow sustainable fisheries, based on resources embedded in functional, diverse ecosystems.  相似文献   
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Managing a rare species can be improved with knowledge of its natural history. The sheepnose (Plethobasus cyphyus) is a freshwater mussel recently listed by the US as federally endangered. We used standard methods to study P. cyphyus brooding behaviour, host fishes in the laboratory and under natural conditions, and glochidial morphology. We monitored a population of P. cyphyus in the Chippewa River, WI during spring and summer 2007–2009 and 2011 and found brooding animals between mid-May and early August. Gravid individuals ranged between 5 and 27 yr (mean age ± 1 s.d. = 13 ± 4 yr). Plethobasus cyphyus brooded glochidia in outer gills, which varied in colour from red, orange, pink, cream, or white. We observed mature glochidia more commonly in individuals with cream or white gills and these glochidia were released in a clear, adhesive, mucus matrix. In laboratory trials we found several minnow and topminnow species (29 spp.) served as productive suitable native hosts. The mean number of juvenile mussels released per cyprinid per day was significantly higher for trials conducted at 22–25°C compared with those at 18–20°C, and 83% of trials conducted at 18–20°C using suitable host species produced no juveniles. Glochidia had a unique outline and shell morphometrics that distinguished P. cyphyus from seven other Chippewa River mussel species that produce similar sized glochidia. Using morphometrics we determined that mimic shiners (Notropis volucellus) were natural hosts for P. cyphyus, round pigtoe (Pleurobema sintoxia), and Wabash pigtoe (Fusconaia flava). Releasing mucus-bound glochidia has evolved in a variety of mussel species and may be more common than is currently realized. Our data show that P. cyphyus is a cyprinid host specialist, and propagation efforts for this species can be strengthened through improved access to mature glochidia by using females with cream-coloured gills and increased juvenile production through warmer fish holding temperatures.  相似文献   
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