Across the tropics, smallholder farmers already face numerous risks to agricultural production. Climate change is expected to disproportionately affect smallholder farmers and make their livelihoods ...even more precarious; however, there is limited information on their overall vulnerability and adaptation needs. We conducted surveys of 600 households in Madagascar to characterize the vulnerability of smallholder farmers, identify how farmers cope with risks and explore what strategies are needed to help them adapt to climate change. Malagasy farmers are particularly vulnerable to any shocks to their agricultural system owing to their high dependence on agriculture for their livelihoods, chronic food insecurity, physical isolation and lack of access to formal safety nets. Farmers are frequently exposed to pest and disease outbreaks and extreme weather events (particularly cyclones), which cause significant crop and income losses and exacerbate food insecurity. Although farmers use a variety of risk-coping strategies, these are insufficient to prevent them from remaining food insecure. Few farmers have adjusted their farming strategies in response to climate change, owing to limited resources and capacity. Urgent technical, financial and institutional support is needed to improve the agricultural production and food security of Malagasy farmers and make their livelihoods resilient to climate change.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Efficient protein turnover is essential for cellular homeostasis and organ function. Loss of proteostasis is a hallmark of aging culminating in severe dysfunction of protein turnover. To investigate ...protein turnover dynamics as a function of age, we performed continuous in vivo metabolic stable isotope labeling in mice along the aging continuum. First, we discovered that the brain proteome uniquely undergoes dynamic turnover fluctuations during aging compared to heart and liver tissue. Second, trends in protein turnover in the brain proteome during aging showed sex-specific differences that were tightly tied to cellular compartments. Next, parallel analyses of the insoluble proteome revealed that several cellular compartments experience hampered turnover, in part due to misfolding. Finally, we found that age-associated fluctuations in proteasome activity were associated with the turnover of core proteolytic subunits, which was recapitulated by pharmacological suppression of proteasome activity. Taken together, our study provides a proteome-wide atlas of protein turnover across the aging continuum and reveals a link between the turnover of individual proteasome subunits and the age-associated decline in proteasome activity.
Synopsis
Continuous pulse-step metabolic labeling with quantitative proteomics in mice reveals sex-specific differences in protein turnover linked to subcellular compartments. Age-related changes in protein turnover result in part from altered proteasome activity and subunit turnover.
Brain protein turnover trends during aging display sex-specific differences tied to subcellular compartments.
Misfolded proteins contribute to differential turnover trends in the brain.
Reduced proteasome activity is associated with slowed turnover of proteasome subunits during aging.
Continuous pulse-step metabolic labeling with quantitative proteomics in mice reveals sex-specific differences in protein turnover linked to subcellular compartments. Age-related changes in protein turnover result in part from altered proteasome activity and subunit turnover.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Toxic amyloid-beta (Aβ) peptides, produced by sequential proteolytic cleavage of the amyloid precursor protein (APP), play a key role in the initial stage of Alzheimer’s disease (AD). Increasing ...evidence indicates that Aβ42 induces neuronal circuit hyperexcitability in the early stages of AD pathology. As a result, researchers have investigated treatments that modulate the excitatory/inhibitory imbalance as potential AD therapies. For example, levetiracetam, an atypical antiepileptic drug used to quell hyperexcitability, has garnered recent interest in the AD field, even though its exact mechanism(s) of action remains elusive. Here, we show that in APP knock-in mouse models of amyloid pathology, chronic levetiracetam administration decreases cortical Aβ42 levels and lowers the amyloid plaque burden. In addition, using multiplexed tandem mass tag-quantitative mass spectrometry-based proteomic analysis, we determined that chronic levetiracetam administration selectively normalizes levels of presynaptic endocytic proteins. Finally, we found that levetiracetam treatment selectively lowers beta carboxyl-terminal fragment levels, while the abundance of full-length APP remains unchanged. In summary, this work reports that chronic treatment with levetiracetam serves as a useful therapeutic in AD by normalizing levels of presynaptic endocytic proteins and altering APP cleavage preference, leading to a decrease in both Aβ42 levels and the amyloid plaque burden. These novel findings provide novel evidence for the previously documented therapeutic value of levetiracetam to mitigate AD pathology.
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IJS, KILJ, NUK, PNG, UL, UM
The accumulation of amyloid beta (Aβ) peptides in fibrils is prerequisite for Alzheimer's disease (AD). Our understanding of the proteins that promote Aβ fibril formation and mediate neurotoxicity ...has been limited due to technical challenges in isolating pure amyloid fibrils from brain extracts.
To investigate how amyloid fibrils form and cause neurotoxicity in AD brain, we developed a robust biochemical strategy. We benchmarked the success of our purifications using electron microscopy, amyloid dyes, and a large panel of Aβ immunoassays. Tandem mass-spectrometry based proteomic analysis workflows provided quantitative measures of the amyloid fibril proteome. These methods allowed us to compare amyloid fibril composition from human AD brains, three amyloid mouse models, transgenic Aβ42 flies, and Aβ42 seeded cultured neurons.
Amyloid fibrils are primarily composed by Aβ42 and unexpectedly harbor Aβ38 but generally lack Aβ40 peptides. Multidimensional quantitative proteomics allowed us to redefine the fibril proteome by identifying 20 new amyloid-associated proteins. Notably, we confirmed 57 previously reported plaque-associated proteins. We validated a panel of these proteins as bona fide amyloid-interacting proteins using antibodies and orthogonal proteomic analysis. One metal-binding chaperone metallothionein-3 is tightly associated with amyloid fibrils and modulates fibril formation in vitro. Lastly, we used a transgenic Aβ42 fly model to test if knock down or over-expression of fibril-interacting gene homologues modifies neurotoxicity. Here, we could functionally validate 20 genes as modifiers of Aβ42 toxicity in vivo.
These discoveries and subsequent confirmation indicate that fibril-associated proteins play a key role in amyloid formation and AD pathology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
5.
Mapping global human dependence on marine ecosystems Selig, Elizabeth R.; Hole, David G.; Allison, Edward H. ...
Conservation letters,
March/April 2019, 2019-03-00, 20190301, Volume:
12, Issue:
2
Journal Article
Peer reviewed
Open access
Many human populations are dependent on marine ecosystems for a range of benefits, but we understand little about where and to what degree people rely on these ecosystem services. We created a new ...conceptual model to map the degree of human dependence on marine ecosystems based on the magnitude of the benefit, susceptibility of people to a loss of that benefit, and the availability of alternatives. We focused on mapping nutritional, economic, and coastal protection dependence, but our model is repeatable, scalable, applicable to other ecosystems, and designed to incorporate additional services and data. Here we show that dependence was highest for Pacific and Indian Ocean island nations and several West African countries. More than 775 million people live in areas with relatively high dependence scores. By identifying where and how people are dependent on marine ecosystems, our framework can be used to design more effective large‐scale management and policy interventions.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
► Ecosystem services are useful for assessing trade-offs in water quality management. ► We trialled the approach in the Tully–Murray catchment, Great Barrier Reef and found. ► Trade-offs between food ...production, water quality regulation, tourism and fisheries. ► Symmetry between private stakeholders: farmers, tour operators, tourists and fishermen. ► Scale mis-matches between ecosystem service flows and water quality governance.
The Great Barrier Reef (GBR), Australia, is threatened by declining water quality largely derived from agricultural run-off. Water quality planning aims to mitigate pollutant run-off through land management, including riparian and wetland restoration, but no tools exist to assess trade-offs in land use change across the catchment-to-reef continuum. We adapted the Millennium Ecosystem Assessment framework in the GBR's Tully–Murray catchment to identify trade-offs between linked ecosystem services and stakeholders. Applying four land use scenarios we assessed outcomes for the ecosystem service of water quality regulation, and trade-offs with six floodplain services and four GBR services. Based on statistical correlations between ecosystem services’ status under the scenarios, we identified trade-offs and thresholds between services and associated stakeholders. The most direct trade-off in floodplain services (and primary stakeholders) was food and fibre production (farmers) versus water quality regulation (community, GBR tourists, tour operators and fishermen). There were synergies between water quality regulation (community, GBR tourists, tour operators and fishermen) and floodplain recreational and commercial fisheries (fishermen). Scale mis-matches between water quality management structures and ecosystem service flows were also evident. We discuss the strengths and weaknesses of this ecosystem services approach, and its potential application in the GBR and other catchment-to-reef social–ecological systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Electron tomography of the chemical synapse provides important architectural information regarding the organization of synaptic organelles including synaptic vesicles, Nissl bodies, and early ...endosomes. Here, we describe methods for the preparation of select murine brain regions for high-pressure freezing, freeze substitution, and EM tomographic analysis of synaptic structures. The method uses fresh brain slices prepared using a vibratome and biopsy punches to collect specific brain regions of interest suitable for subsequent preservation and EM tomographic imaging.
Abstract Staphylcoccus decolonization prior to surgery is used to prevent surgical site infections (SSIs) after total joint arthroplasty (TJA). To determine if current treatment protocols result in ...successful decolonization of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA), 106 consecutive patients were screened for nasal MSSA/MRSA colonization pre-operatively and on the day of surgery. Colonized patients used intranasal mupirocin twice a day and chlorhexidine showers daily 5 days prior to surgery. Pre-operatively, 24 joints (22.0%) were positive for MSSA colonization and 5 joints (4.6%) were positive for MRSA colonization. On the day of surgery, 3 joints (2.8%) who underwent decolonization were positive for MSSA colonization and 0 joints were positive for MRSA colonization. The reduction in MSSA colonization was significant ( P < 0.001), while the eradication of MRSA colonization approached statistical significance ( P = 0.063). Current decolonization protocols using intranasal mupirocin and chlorhexidine washes are effective for reducing MRSA/MSSA colonization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Autism is characterized by difficulties in social interaction, communication, and repetitive behaviors; with different degrees of severity in each of the core areas. Haploinsufficiency and point ...mutations of
are associated with Smith-Magenis syndrome (SMS), a genetic condition that scores within the autism spectrum range for social responsiveness and communication, and is characterized by neurobehavioral abnormalities, intellectual disability, developmental delay, sleep disturbance, and self-injurious behaviors.
To investigate the relationship between
and social impairment, we evaluated the
mice with a battery of tests to address social behavior in mice.
We found that the mutant mice showed diminished interest in social odors, abnormal submissive tendencies, and increased repetitive behaviors when compared to wild type littermates.
These findings suggest that
contributes to social behavior in mice, and prompt it as a candidate gene for the social behaviors observed in Smith-Magenis Syndrome patients.
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