2,240 research outputs found

    Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2.

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    BACKGROUND: It is becoming increasingly evident that deficits in the cortex and hippocampus at early stages of dementia in Alzheimer's disease (AD) are associated with synaptic damage caused by oligomers of the toxic amyloid-β peptide (Aβ42). However, the underlying molecular and cellular mechanisms behind these deficits are not fully understood. Here we provide evidence of a mechanism by which Aβ42 affects synaptic transmission regulating neurotransmitter release. METHODOLOGY/FINDINGS: We first showed that application of 50 nM Aβ42 in cultured neurones is followed by its internalisation and translocation to synaptic contacts. Interestingly, our results demonstrate that with time, Aβ42 can be detected at the presynaptic terminals where it interacts with Synaptophysin. Furthermore, data from dissociated hippocampal neurons as well as biochemical data provide evidence that Aβ42 disrupts the complex formed between Synaptophysin and VAMP2 increasing the amount of primed vesicles and exocytosis. Finally, electrophysiology recordings in brain slices confirmed that Aβ42 affects baseline transmission. CONCLUSIONS/SIGNIFICANCE: Our observations provide a necessary and timely insight into cellular mechanisms that underlie the initial pathological events that lead to synaptic dysfunction in Alzheimer's disease. Our results demonstrate a new mechanism by which Aβ42 affects synaptic activity

    Case studies on the socio-economic characteristics and lifestyles subsistence and informal fisheries in South Africa

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    To develop a management strategy for informal fishers, a necessary first step is information about the nature of these fishers, their numbers and their socio-economic status. To accomplish this, a survey of socio-economic conditions and use of marine resources was undertaken in 1999 at 20 localities where fishing occurs around the coast of South Africa, concentrating on subsistence or small- to micro-scale artisanal commercial fishers. In each locality, 16–31 “fisher households” were surveyed by questionnaires, focus-group discussions and interviews with key informants. Demographic analyses revealed a low level of migrancy (~5%), an average of 5.3 persons per household and a mean age of 27. Only ~20% of fishers were women and ~15% were children. Poverty was prevalent: unemployment averaged 40.3% (much higher than the national norm of 29.3%). Mean adult equivalent income per month spanned R193–R735 among regions, and was not correlated with size of settlement. Education levels were low, only ~33% of people >20 years old having completed primary school. Migrancy was highest in rural areas (but still much less than the national norm), intermediate in towns and least in metropolitan areas. Household size, participation of women and poverty all followed similar trends. Comparing regions, the East Coast and the province of KwaZulu-Natal had higher migrancy rates, larger household sizes, greater poverty, and greater participation by women in fishing, than on the South and West coasts. Household expenditure on food was ~R450 per month on the South-East and KwaZulu-Natal coasts and ~R750 on the West Coast, and exceeded 60% of income (a measure of “food security”) in about half the households surveyed. Harvested resources were sold, consumed or used as bait. In all regions, the two most frequently harvested resources were fish (mostly sold, predominantly fished by men) and intertidal rocky-shore invertebrates (largely consumed, and involving women to a greater degree). On the West Coast, rock lobster Jasus lalandii was the third-most important resource, but on the South and KwaZulu-Natal coasts this species was replaced by estuarine invertebrates. Abalone Haliotis midae, oysters, sandy-beach invertebrates and kelp or seaweeds made up the balance. Diversity of harvested resources increased west to east, following biogeographic trends. The resources could be divided into those of high value (rock lobsters, abalone and, to a lesser extent, fish) and those of lower value (such as limpets, mussels and bait organisms). It is argued that high-value resources are best used to create micro- and small-scale commercial enterprises that can serve to uplift poor fishers. Lowvalue resources constitute subsistence resources, for which preferential rights should be established for subsistence fishers, including development of exclusive-use zones where necessary. Emerging characteristics of fishing communities that were helpful in defining subsistence fishers in the South African context were poverty, harvest for self-use (whether by consumption or sale to meet basic needs of food security), use of low-technology gear, and concentration of effort on or from shores or in estuaries. At least portions of the catches of all resources are sold, and the majority of equipment is purchased, so any definition of subsistence fishers cannot exclude those who sell part of their catch or do not use hand-made equipment. Some success was evident with co-management, encouraging further exploration of this style of management for subsistence fishers. Keywords: informal fishers, socio-economics of fishers, subsistence fishersAfrican Journal of Marine Science 2002, 24: 439–46

    Assessment of resource availability and sustainability for subsistence fishers in South Africa, with a review of resource management procedures

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    The availability of resources and their suitability for subsistence and small-scale commercial fishers in South Africa were assessed and appropriate options for the management of resources recommended. Assessment of current resource utilization and recommendations for future subsistence and/or small-scale commercial use were based on information gathered during a nationwide survey of 144 subsistence fishing communities in South Africa and a review of relevant published and unpublished literature. Current patterns of resource use in three regions of the coast (West, South and East coasts) revealed that most true subsistence fisheries occur in the eastern half of the country. These fisheries are primarily focused on invertebrate species found on intertidal rocky shores and sandy beaches, or in estuaries. Fish are harvested by rod or handline, netting or traditional fishing methods (fishtraps, spearing, baited baskets). No “new” or previously underutilized resources were identified as suitable for subsistence fishing in any of the three regions. The potential for several new small-scale commercial fisheries was identified, but the need to retain certain resources for subsistence fisheries (rather than converting them to small-scale commercial fisheries) was evident in certain areas. Resources with high commercial value were not considered suitable for subsistence fishing, but rather for the introduction of small-scale commercial fisheries. The overall management strategy for the subsistence sector, which is currently in the process of being developed, must ensure sufficient flexibility to be able to take into account regional and site-specific requirements. It will also need to develop co-management structures, protect traditional fishing practices, avoid user conflict and provide for no-take areas, all within the framework of sustainable resource utilization.Keywords: estuarine resources, fisheries management, intertidal resources, subsistence fisheries, subtidal resourcesAfrican Journal of Marine Science 2002, 24: 489–50

    Perceptions of subsistence and informal fishers in South Africa regarding the management of living marine resources

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    Following the legal recognition of subsistence fishers in 1998 through the promulgation of the Marine Living Resources Act, a Subsistence Fisheries Task Group (SFTG) was appointed by national government to provide recommendations on the management of subsistence fishing in South Africa. To achieve effective management, the SFTG recognized that fishers' needs, perceptions and concerns must be understood and incorporated into future management strategies. As a result, information from fishers was gathered through a five-month research programme that included questionnaire surveys, focus-group meetings, a “roadshow” and a national workshop. Research findings indicated that the fishers' responses centred on four key themes related to (1) the criteria for defining a subsistence fisher, (2) current management practices, (3) resource use and (4) livelihood strategies. Feedback from fishers revealed several issues that have led to uncertainty and dissatisfaction among informal and subsistence fishers. However, these perceptions need to be contextualized within the historical circumstances of fisheries management in South Africa, and it must be recognized that attitudes will only change when management approaches embrace the needs, perceptions and concerns of the users. The information outlined in this paper was instrumental in guiding the formulation of the SFTG recommendations regarding the definition of subsistence fishers and their future management in South Africa.Keywords: fisheries management, perceptions about fisheries, subsistence fishersAfrican Journal of Marine Science 2002, 24: 463–47

    Tie-2 regulates the stemness and metastatic properties of prostate cancer cells.

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    Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis.published_or_final_versio

    Development and characterisation of microsatellite loci in Eucalyptus globulus (Myrtaceae)

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    Eucalyptus globulus Labill. is the premier hardwood plantation species in temperate regions of the world. We developed twelve E. globulus microsatellite loci for fingerprinting and future studies in genome mapping, gene flow and genetic diversity. The microsatellites were highly polymorphic in E. globulus (average number of alleles per locus, 17.8; average observed heterozygosity, 0.66). The loci were robust, amplifying in other Eucalyptus species, Corymbia and Angophora. The high variability and transferability of these molecular markers make them useful in E. globulus, as well as in many of the 700 species of Eucalyptus

    An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

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    ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153USversus187US versus 187US per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly
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