946 research outputs found
The Non-Canonical Wnt/PKC Pathway Regulates Mitochondrial Dynamics through Degradation of the Arm-Like Domain-Containing Protein Alex3
The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation
Synergies for Improving Oil Palm Production and Forest Conservation in Floodplain Landscapes
Lowland tropical forests are increasingly threatened with conversion to oil palm as global demand and high profit drives crop expansion throughout the world’s tropical regions. Yet, landscapes are not homogeneous and regional constraints dictate land suitability for this crop. We conducted a regional study to investigate spatial and economic components of forest conversion to oil palm within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo. The Kinabatangan ecosystem harbours significant biodiversity with globally threatened species but has suffered forest loss and fragmentation. We mapped the oil palm and forested landscapes (using object-based-image analysis, classification and regression tree analysis and on-screen digitising of high-resolution imagery) and undertook economic modelling. Within the study region (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net-Present-Value (NPV) estimates (637/ha?yr); but 20.5% is under-producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with negative NPV of -65/ha?yr) due to palm mortality from flood inundation. These areas would have been important riparian or flooded forest types. Moreover, 30,173 ha of unprotected forest remain and despite its value for connectivity and biodiversity 64% is allocated for future oil palm. However, we estimate that at minimum 54% of these forests are unsuitable for this crop due to inundation events. If conversion to oil palm occurs, we predict a further 16,207 ha will become commercially redundant. This means that over 32,000 ha of forest within the floodplain would have been converted for little or no financial gain yet with significant cost to the ecosystem. Our findings have globally relevant implications for similar floodplain landscapes undergoing forest transformation to agriculture such as oil palm. Understanding landscape level constraints to this crop, and transferring these into policy and practice, may provide conservation and economic opportunities within these seemingly high opportunity cost landscapes
Assessment of the load-velocity profile in the free-weight prone bench pull exercise through different velocity variables and regression models
This aims of this study were (I) to determine the velocity variable and regression model which best fit the load-velocity relationship during the free-weight prone bench pull exercise, (II) to compare the reliability of the velocity attained at each percentage of the one-repetition maximum (1RM) between different velocity variables and regression models, and (III) to compare the within- and between-subject variability of the velocity attained at each %1RM. Eighteen men (14 rowers and four weightlifters) performed an incremental test during the free-weight prone bench pull exercise in two different sessions. General and individual load-velocity relationships were modelled through three velocity variables (mean velocity [MV], mean propulsive velocity [MPV] and peak velocity [PV]) and two regression models (linear and second-order polynomial). The main findings revealed that (I) the general (Pearson's correlation coefficient [r] range = 0.964-0.973) and individual (median r = 0.986 for MV, 0.989 for MPV, and 0.984 for PV) load-velocity relationships were highly linear, (II) the reliability of the velocity attained at each %1RM did not meaningfully differ between the velocity variables (coefficient of variation [CV] range = 2.55-7.61% for MV, 2.84-7.72% for MPV and 3.50-6.03% for PV) neither between the regression models (CV range = 2.55-7.72% and 2.73-5.25% for the linear and polynomial regressions, respectively), and (III) the within-subject variability of the velocity attained at each %1RM was lower than the between-subject variability for the light-moderate loads. No meaningful differences between the within- and between-subject CVs were observed for the MV of the 1RM trial (6.02% vs. 6.60%; CVratio = 1.10), while the within-subject CV was lower for PV (6.36% vs. 7.56%; CVratio = 1.19). These results suggest that the individual load-MV relationship should be determined with a linear regression model to obtain the most accurate prescription of the relative load during the free-weight prone bench pull exercise
A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach
AIMS
To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes.
METHODS
We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals.
RESULTS
The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment.
CONCLUSIONS
We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way
Bioenergy production and sustainable development: science base for policymaking remains limited
The possibility of using bioenergy as a climate change mitigation measure has sparked a discussion of whether and how bioenergy production contributes to sustainable development. We undertook a systematic review of the scientific literature to illuminate this relationship and found a limited scientific basis for policymaking. Our results indicate that knowledge on the sustainable development impacts of bioenergy production is concentrated in a few well-studied countries, focuses on environmental and economic impacts, and mostly relates to dedicated agricultural biomass plantations. The scope and methodological approaches in studies differ widely and only a small share of the studies sufficiently reports on context and/or baseline conditions, which makes it difficult to get a general understanding of the attribution of impacts. Nevertheless, we identified regional patterns of positive or negative impacts for all categories – environmental, economic, institutional, social and technological. In general, economic and technological impacts were more frequently reported as positive, while social and environmental impacts were more frequently reported as negative (with the exception of impacts on direct substitution of GHG emission from fossil fuel). More focused and transparent research is needed to validate these patterns and develop a strong science underpinning for establishing policies and governance agreements that prevent/mitigate negative and promote positive impacts from bioenergy production
Practical procedure for discriminating monofloral honey with a broad pollen profile variability using an electronic tongue
Colour and floral origin are key parameters that may influence the honey market. Monofloral light honey are more demanded by consumers, mainly due to their flavour, being more valuable for producers due to their higher price when compared to darker honey. The latter usually have a high anti-oxidant content that increases their healthy potential. This work showed that it is possible to correctly classify monofloral honey with a high variability in floral origin with a potentiometric electronic tongue after making a preliminary selection of honey according their colours: white, amber and dark honey. The results showed that the device had a very satisfactory sensitivity towards floral origin (Castanea sp., Echium sp., Erica sp., Lavandula sp., Prunus sp. and Rubus sp.), allowing a leave-one-out cross validation correct classification of 100%. Therefore, the E-tongue shows potential to be used at analytical laboratory level for honey samples classification according to market and quality parameters, as a practical tool for ensuring monofloral honey authenticity
Process evaluation in the field: global learnings from seven implementation research hypertension projects in low-and middle-income countries
Background
Process evaluation is increasingly recognized as an important component of effective implementation research and yet, there has been surprisingly little work to understand what constitutes best practice. Researchers use different methodologies describing causal pathways and understanding barriers and facilitators to implementation of interventions in diverse contexts and settings. We report on challenges and lessons learned from undertaking process evaluation of seven hypertension intervention trials funded through the Global Alliance of Chronic Diseases (GACD).
Methods
Preliminary data collected from the GACD hypertension teams in 2015 were used to inform a template for data collection. Case study themes included: (1) description of the intervention, (2) objectives of the process evaluation, (3) methods including theoretical basis, (4) main findings of the study and the process evaluation, (5) implications for the project, policy and research practice and (6) lessons for future process evaluations. The information was summarized and reported descriptively and narratively and key lessons were identified.
Results
The case studies were from low- and middle-income countries and Indigenous communities in Canada. They were implementation research projects with intervention arm. Six theoretical approaches were used but most comprised of mixed-methods approaches. Each of the process evaluations generated findings on whether interventions were implemented with fidelity, the extent of capacity building, contextual factors and the extent to which relationships between researchers and community impacted on intervention implementation. The most important learning was that although process evaluation is time consuming, it enhances understanding of factors affecting implementation of complex interventions. The research highlighted the need to initiate process evaluations early on in the project, to help guide design of the intervention; and the importance of effective communication between researchers responsible for trial implementation, process evaluation and outcome evaluation.
Conclusion
This research demonstrates the important role of process evaluation in understanding implementation process of complex interventions. This can help to highlight a broad range of system requirements such as new policies and capacity building to support implementation. Process evaluation is crucial in understanding contextual factors that may impact intervention implementation which is important in considering whether or not the intervention can be translated to other contexts
A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary
BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease
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