Aquaporins in brain edema Clément, Tifenn; Rodriguez‐Grande, Beatriz; Badaut, Jérôme
Journal of neuroscience research,
January 2020, Volume:
98, Issue:
1
Journal Article
Peer reviewed
Open access
Brain edema is a common feature of brain injuries, which leads to increased intracranial pressure (ICP) and ischemia that worsen outcome. Current management of edema focuses on reduction of ICP, but ...there are no treatments targeting the molecular players directly involved in edema process. The perivascular astrocyte endfeet are critical in maintaining brain homeostasis with ionic and water exchange; in this context, aquaporins (AQPs), astrocyte water channels, have emerged as privileged targets for edema modulation. However, AQPs can facilitate either accumulation or drainage of water, depending on the osmotic gradients between extra‐intracellular space; and thus inhibition of AQPs leads to different outcomes depending on specific tissue characteristics and time post‐injury. Most of this knowledge has been gathered from the study of AQP4, the best characterized AQP and the one that has the biggest impact on water movement. In addition to the level of expression, the ratio of AQP4 isoforms (m1, m23 or mz), the spatial distribution of AQP4 into orthogonal arrays of particles, and the interaction of AQP4 with neighboring ionic channels and gap junctions could directly impact edema formation. Although there are no specific AQP4 pharmacological blockers, the development of AQP4 siRNA offers a promising therapeutic tool. Given the complex dynamics of AQP4, therapies targeting AQP4 should carefully take into account the particular features of the injury (e.g., hemorrhagic vs. non‐hemorrhagic) and different times after injury (e.g., phase of edema formation vs. resolution).
Following brain injury, the astrocyte water channel AQP4 mediates edema formation and resolution. Several factors modulate the actions of AQP4 including: (a) AQP4 membrane distribution into arrays, depending on the ratio of AQP4 isoforms; (b) AQP4 interactions with ion channels and gap junctions; (c) temporal variations in AQP4 expression.
Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to ...be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.
Abstract
Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define ...these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus, coxsackievirus B3. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide a comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.
Degrowth: from theory to practice Sekulova, Filka; Kallis, Giorgos; Rodríguez-Labajos, Beatriz ...
Journal of cleaner production,
January 2013, 2013, 2013-1-00, 20130101, Volume:
38
Journal Article
Peer reviewed
The collection of articles reviewed in this editorial presents an eclectic sample of the best contributions from the Second international conference on degrowth, exemplifying recent debates in the ...field and touching on different aspects of the multi-dimensional transition at stake. Moving beyond theory and the construction of the degrowth proposal, the articles in this special issue look at particular applications, new methodologies and fresh policy options. For example, social enterprises are evaluated as primer candidates for a sustainable degrowth economy in the North. Lessons are also drawn from very different parts of the world, such as Cuba's experience with an oil and commodity shock, to which it adapted through the introduction of ecological labour-intensive agriculture in urban regions.
This Special Issue approaches from a degrowth perspective important sectoral issues in agriculture, resource consumption and water. The unsustainable fuel-dependence of the Spanish agrarian sector, where the energy input for the production process is six times higher than the energy contained in finished food products, is analysed in the context of the industrialization of food production. Rather than efficiency, sufficiency (in consumption) is proposed as an organising societal principle and a call is made for stronger NGO action and coalition-building in the direction of absolute (rather than relative) consumption reduction. The obstacles to sufficiency policies are illustrated with a case-study on water in the city of Barcelona, where a growth discourse is still dominant and a source of a technological and institutional deadlock against softer, decentralized and more participatory forms of water management.
Finally, many of the contributions in this issue focus on work. The policy option of a Job Guarantee scheme is examined as a tool to decouple jobs from economic growth and fiscal policy by bringing them to the realm of political rights. This is complemented by a discussion of the social benefits of an “amateur economy” through work-sharing and a socially beneficial reduction in labour productivity. Original data from Barcelona analysed for this Special Issue shows that household activities, an essential component of a more amateur economy, have a much lower intensity of energy use than the paid-sector delivery of equivalent services, especially government and privatized caring services. Interesting research questions are identified concerning work under a degrowth trajectory, not least whether reducing paid work will be possible in an energy-scarce future. Put together, the diverse contributions of this issue show that there is a vibrant and fertile degrowth research agenda with a range of open questions to which the community of this journal has much to offer.
Aims:
Our study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify ...youth with maturity-onset diabetes of the young (MODY).
Methods:
The SEARCH for Diabetes in Youth study is a US multicenter, population-based study of youth with diabetes diagnosed at age younger than 20 years. We sequenced genomic DNA for mutations in the HNF1A, HNF4A, and glucokinase genes in 586 participants enrolled in SEARCH between 2001 and 2006. Selection criteria included diabetes autoantibody negativity and fasting C-peptide levels of 0.8 ng/mL or greater.
Results:
We identified a mutation in one of three MODY genes in 47 participants, or 8.0% of the tested sample, for a prevalence of at least 1.2% in the pediatric diabetes population. Of these, only 3 had a clinical diagnosis of MODY, and the majority was treated with insulin. Compared with the MODY-negative group, MODY-positive participants had lower FCP levels (2.2 ± 1.4 vs 3.2 ± 2.1 ng/mL, P < .01) and fewer type 2 diabetes-like metabolic features. Parental history of diabetes did not significantly differ between the 2 groups.
Conclusions/Interpretation:
In this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.
RNA viruses have notoriously high mutation rates due to error-prone replication by their RNA polymerase. However, natural selection concentrates variability in a few key viral proteins. To test ...whether this stems from different mutation tolerance profiles among viral proteins, we measured the effect of >40,000 non-synonymous mutations across the full proteome of coxsackievirus B3 as well as >97% of all possible codon deletions in the nonstructural proteins. We find significant variation in mutational tolerance within and between individual viral proteins, which correlated with both general and protein-specific structural and functional attributes. Furthermore, mutational fitness effects remained stable across cell lines, suggesting selection pressures are mostly conserved across environments. In addition to providing a rich dataset for understanding virus biology and evolution, our results illustrate that incorporation of mutational tolerance data into druggable pocket discovery can aid in selecting targets with high barriers to drug resistance.
This article explores the political project of the Afro-Ecuadorian Ancestral Territory of Imbabura and Carchi, advanced by the members of the Coordinadora Nacional de Mujeres Negras del Ecuador ...(CONAMUNE; National Coordination of Black Women of Ecuador) in the northern Ecuadorian highlands. I show how Black women resignify their past and assert their sense of place in an Andean region widely considered Indigenous. That region is marked by racial exploitation and land dispossession, and the political project of nation-building based on the ideology of mestizaje. Black women of CONAMUNE create a space for dialogue between Afrodescendant social organizations and the state, while engaging with Indigenous territorial projects. These Black women strengthen and mobilize diasporic identities by emphasizing the African blood spilled on the soil by their ancestors and the participation of Black enslaved women in the struggle for freedom. I argue that the Ancestral Territory project entails an ongoing geographic struggle in which Afrodescendant women create a particular sense of place as they live and imagine a geography of resistance.
Objectives
To investigate a possible relationship between altered nasal flow and chronic otitis media (COM) using computational fluid dynamics (CFD).
Study Design
Retrospective case series.
Methods
...Retrospective cohort sample of CT scans from patients with COM and controls without COM to compare the results of various nasal airflow parameters determined by CFD between a group of patients with COM (N = 60) and a control group of subjects without any evidence of ear disease (N = 81).
The CT were subjected to various procedures to carry out CFD studies, determining the resistance to nasal flow, the proportion of flow through the right and left nasal cavity, and two nondimensional estimators. The results of CFD studies between patients with COM and controls were compared.
Results
Whereas only 12.3% of the controls had CFD alteration (10 out of 81), 43.3% of the patients suffering COM displayed alterations of our nondimensional parameters R−ϕ (26 out of 60).
Conclusions
According to our results, the incidence of alterations in nasal airflow by studying with CFD is significantly higher in patients with COM than in controls. To our knowledge, this is the first article linking nasal cavity and COM using a CFD approach. Our results support the hypothesis that nasal flow alterations could be implicated in the etiopathogenesis of the COM.
Level of Evidence
4 Laryngoscope, 132:1224–1230, 2022
In 2020, the Global Media Monitoring Project (GMMP) marked its silver anniversary by releasing its sixth report on the representation of women in the global media landscape, and in 2021, the NGO Plan ...International unveiled the tenth edition of its report “State of the World’s Girls: The Truth Gap”. The study focused on how misinformation impacts equal opportunities for girls, adolescents, and young women worldwide, and proposed strategies to combat the “truth gap”. These examples showcase the collective efforts made in recent decades by professionals, academia, institutions, NGOs, and activists to enhance the state of information globally. The aspiration is ambitious, aiming to make information more transparent, accessible, and inclusive, fostering equality, truth-seeking, and the visibility of women, young people, and rural populations. However, the findings from the GMMP reports, as well as the analysis conducted by Plan International and numerous other works, underscore that despite evident social changes worldwide—particularly in the educational, labor, and social realms for women—access to truthful and high-quality information remains elusive. Simultaneously, studies reveal a declining public trust, especially among young people, in traditional media, a shift to alternative information sources, and a deterioration in the quality benchmarks of the journalism profession. Journalism, a pursuit of truth from sources to the public, has historically been and should remain a pillar upholding democracy and freedom. This article employs a qualitative case study methodology to analyze the best practices proposed across various domains to safeguard information quality. Special attention is given to initiatives that aim to involve women and young people in the collective effort against misinformation.
The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and ...Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.
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