Background. Progressive multifocal leukoencephalopathy (PML) is a rare, severe, otherwise fatal viral infection of the white matter of the brain caused by the polyomavirus JC virus, which typically ...occurs only in immunocompromised patients. One patient with dominant gain-of-function (GOF) mutation in signal transducer and activator of transcription 1 (STAT1) with chronic mucocutaneous candidiasis and PML was reported previously. We aim to identify the molecular defect in 3 patients with PML and to review the literature on PML in primary immune defects (PIDs). Methods. STAT1 was sequenced in 3 patients with PML. U3C cell lines were transfected with STAT1 and assays to search for STAT1 phosphorylation, transcriptional response, and target gene expression were performed. Results. We identified 3 new unrelated cases of PML in patients with GOF STAT1 mutations, including the novel STAT1 mutation, L400Q. These STAT1 mutations caused delayed STAT1 dephosphorylation and enhanced interferon-gamma–driven responses. In our review of the literature regarding PML in primary immune deficiencies we found 26 cases, only 54% of which were molecularly characterized, the remainder being syndromically diagnosed only. Conclusions. The occurrence of PML in 4 cases of STAT1 GOF suggests that STAT1 plays a critical role in the control of JC virus in the central nervous system.
Access to adequate quantity and quality of fresh water is critical to the well-being of Tanzania’s human population, currently approaching 50 million. In the early 2000s, Tanzania revamped its legal ...and institutional frameworks related to freshwater resources management with the passage of the National Water Policy (NAWAPO) and the Water Resources Management (WRM) Act. Three major components of these frameworks are: the use of natural hydrological boundaries as units for management; the designation of an order for decision making on water allocation that prioritizes basic human and ecosystem water needs; and the encouragement of community participation in freshwater resources management. Institutionally, WRM now follows a nested approach, with the Tanzanian Ministry of Water operating at a national scale, nine basin water offices responsible for water allocation at a river basin scale, and formally recognized water users’ associations as mechanisms for public participation at the catchment scale. To date, 93 water users’ associations have been formed. Although some are active and appear effective, others are almost dormant, and not achieving their full potential as partners in WRM. In this paper, we provide context for the sweeping changes in WRM in Tanzania and review the lessons from more than a decade of implementation of the NAWAPO. We focus in particular on the role of the water users’ associations, and use case studies of three basins—the Pangani, Wami/Ruvu, and Lake Victoria—to examine their strengths and challenges. Tanzania’s experience offers lessons for other countries considering revision to legal and institutional frameworks around fresh water.
Conserving Brazil's free-flowing rivers Fernandes, Stephannie; Couto, Thiago B A; Ferreira, Manuel ...
Science (American Association for the Advancement of Science),
2023-Mar-03, 2023-03-03, 20230303, Letnik:
379, Številka:
6635
Journal Article
River flows connect people, places, and other forms of life, inspiring and sustaining diverse cultural beliefs, values, and ways of life. The concept of environmental flows provides a framework for ...improving understanding of relationships between river flows and people, and for supporting those that are mutually beneficial. Nevertheless, most approaches to determining environmental flows remain grounded in the biophysical sciences. The newly revised Brisbane Declaration and Global Action Agenda on Environmental Flows (2018) represents a new phase in environmental flow science and an opportunity to better consider the co‐constitution of river flows, ecosystems, and society, and to more explicitly incorporate these relationships into river management. We synthesize understanding of relationships between people and rivers as conceived under the renewed definition of environmental flows. We present case studies from Honduras, India, Canada, New Zealand, and Australia that illustrate multidisciplinary, collaborative efforts where recognizing and meeting diverse flow needs of human populations was central to establishing environmental flow recommendations. We also review a small body of literature to highlight examples of the diversity and interdependencies of human‐flow relationships—such as the linkages between river flow and human well‐being, spiritual needs, cultural identity, and sense of place—that are typically overlooked when environmental flows are assessed and negotiated. Finally, we call for scientists and water managers to recognize the diversity of ways of knowing, relating to, and utilizing rivers, and to place this recognition at the center of future environmental flow assessments.
This article is categorized under:
Water and Life > Conservation, Management, and Awareness
Human Water > Water Governance
Human Water > Water as Imagined and Represented
For many human populations around the world, river flows are linked to livelihood, identity, sense of place, religious beliefs and ceremonies, language systems, or educational practices. These embedded, reciprocal, and constitutive relationships between humans and rivers remain poorly understood, but can be critically important to assessment and implementation of environmental flows
River rhythmicity refers to the periodic, recurrent phenomena of a riverscape that are synchronized with the rise and fall of river water, creating regimes of river time. River rhythmicity can serve ...as a lens into the temporal dimension of river formation and socio‐ecological dynamics that are of great interest to many disciplines.
In this paper, we introduce river rhythmicity as a conceptual and analytical framework to unify riparian human communities, academic disciplines and water agencies in approaching research and management of rivers. We also explore how the disruptions to riverine rhythms that are experienced by river‐dwelling communities, and are often visible in river discharge data through time, reconfigure, hinder or sever relationships between people and rivers.
To ground our discussion in practical, lived experience, we provide brief descriptions of regimes of river time to demonstrate how rhythmic patterns established with rivers in north‐central Canada and Amazonian Colombia shape the lives of two of our co‐authors. By prioritizing holistic accounts of river rhythms, we can elucidate a fuller range of phenomena and their dynamic interactions, revealing riverscape features that are highly valued by local communities yet not often visible to any one discipline.
Rhythmicity provides a conceptual framework to help address several challenges facing river conservation and water allocation dilemmas. By emphasizing relationality, it serves to (a) move beyond a biophysical framing of human‐nature connectedness by demonstrating that dynamic processes and relationships are constitutive of rivers, not derivative of them; (b) enhance understanding of how the temporal dimensions of riverine relationships and river dwelling are experienced; (c) highlight the socio‐cultural consequences of changes to river time and (d) centre socially embedded relationships with rivers forged from generations of observations of care and reciprocity.
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Resumen
La ritmicidad del río se refiere a los fenómenos periódicos y recurrentes de un paisaje fluvial que se sincronizan con el ascenso y descenso del agua del río, creando regímenes de tiempo de los ríos. La ritmicidad del río puede servir como lente de la dimensión temporal de la formación del río y la dinámica socio‐ecológica que son de gran interés para muchas disciplinas.
En este artículo, presentamos la ritmicidad de los ríos como un marco conceptual y analítico para unificar las comunidades humanas ribereñas, las disciplinas académicas y las agencias de agua al abordar la investigación y la gestión de los ríos. También exploramos cómo las interrupciones en los ritmos fluviales que experimentan las comunidades que habitan en los ríos, y que a menudo son visibles en los datos de descarga del río a lo largo del tiempo, reconfiguran, dificultan o rompen las relaciones entre las personas y los ríos.
Para basar nuestra discusión en una experiencia práctica y vivida, proporcionamos breves descripciones de los regímenes del tiempo de los ríos para demostrar cómo los patrones rítmicos establecidos con los ríos en el centro‐norte de Canadá y la Amazonía de Colombia dan forma a las vidas de dos de nuestros coautores. Al priorizar los relatos holísticos de los ritmos de los ríos, podemos dilucidar una gama más completa de fenómenos y sus interacciones dinámicas, revelando características del paisaje fluvial que son muy valoradas por las comunidades locales pero que a menudo no son visibles para ninguna disciplina.
La ritmicidad proporciona un marco conceptual para ayudar a abordar varios desafíos que enfrentan los dilemas de conservación de ríos y asignación de agua. Enfatizar en la relacionalidad sirve para (i) ir más allá del encuadre biofísico de la conectividad humanos‐naturaleza demostrando que los procesos y relaciones dinámicos son constitutivos de los ríos, no derivados de ellos; (ii) mejorar la comprensión de cómo se experimentan las dimensiones temporales de las relaciones y las viviendas fluviales; (iii) destacar las consecuencias socioculturales de los cambios en el tiempo de los ríos, y (iv) centrar las relaciones socialmente arraigadas con los ríos forjadas a partir de generaciones de observaciones de cuidado y reciprocidad.
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The Amazon River Basin's extraordinary social-ecological system is sustained by various water phases, fluxes, and stores that are interconnected across the tropical Andes mountains, Amazon lowlands, ...and Atlantic Ocean. This "Andes-Amazon-Atlantic" (AAA) pathway is a complex hydroclimatic system linked by the regional water cycle through atmospheric circulation and continental hydrology. Here, we aim to articulate the AAA hydroclimate pathway as a foundational system for research, management, conservation, and governance of aquatic systems of the Amazon Basin. We identify and describe the AAA pathway as an interdependent, multidirectional, and multiscale hydroclimate system. We then present an assessment of recent (1981 to 2020) changes in the AAA pathway, primarily reflecting an acceleration in the rates of hydrologic fluxes (i.e., water cycle intensification). We discuss how the changing AAA pathway orchestrates and impacts social-ecological systems. We conclude with four recommendations for the sustainability of the AAA pathway in ongoing research, management, conservation, and governance.
Correlative evidence suggests that high problem‐solving and foraging abilities in a mate are associated with direct fitness advantages, so it would benefit females to prefer problem‐solving males. ...Recent work has also shown that females of several bird species who directly observe males prefer those that can solve a novel foraging task over those that cannot. In addition to or instead of direct observation of cognitive skills, many species utilize assessment signals when choosing a mate. Here, we test whether females can select a problem‐solving male over a non‐solving male when presented only with a signal known to be used in mate assessment: song. Using an operant conditioning assay, we compared female zebra finch (Taeniopygia guttata) preference for the songs of males that could quickly solve a novel foraging task to the songs of males that could not solve the task. Females were never housed with the test subject males whose song they heard, and the only information provided about the males was their song. We found that females elicited more songs of problem‐solving males than of non‐solvers, indicating that song may contain information about a male’s ability to solve a novel foraging task and that naïve females prefer the songs of problem‐solving males.
Birdsong is known to be an indicator of overall brain function and developmental conditions, but it is unknown whether song can reflect cognitive or personality traits that specifically affect foraging tasks. Here, we tested female preference for song from males who could quickly solve or could not solve an artificial novel foraging task. Although females had no prior knowledge of males, they solicited more song from males who could quickly solve the novel foraging task.
Tuberous sclerosis complex (TSC) is caused by mutations of either the
or
tumor suppressor gene. TSC causes tumors of the brain, heart, kidney, skin and lymphangioleiomyomatosis (LAM). Here we report ...that the TSC2 protein physically binds to high-density lipoprotein binding protein (HDLBP), also called vigilin, a core stress granule (SG) protein, and that TSC2 localizes to SGs. SGs contain mRNAs and translation initiation complexes, and regulate gene expression by sequestering specific transcripts, thereby serving a cytoprotective role. TSC2 has never before been shown to localize to SGs and knocking down vigilin impacts SG translocation of TSC2. TSC2-deficient cells showed a striking increase in the number of SGs after thermal shock and arsenite treatment relative to Tsc2-expressing cells. Our findings also show that murine kidney lysates from a model of TSC have increased levels of SG components including G3BP1 and Caprin1. G3BP1 and Caprin are elevated in renal angiomyolipomas (a renal tumor common in patients with TSC) compared with control normal kidney. G3BP1 is also elevated in TSC-associated subependymal giant cell astrocytomas. We found that genetic inhibition of G3BP1 inhibits the proliferation of TSC2-deficient cells
. Finally, in a mouse model of TSC, genetic inhibition of SGs suppresses cell growth, suggesting that targeting SGs may have efficacy in the therapy of TSC. IMPLICATIONS: This study demonstrates that TSC2 physically interacts with HDLBP/vigilin, a component of SGs, that TSC2 localizes to SG and that TSC2-deficient cells have more SGs, suggesting that SGs represent a novel therapeutic target in TSC.
Dicer is essential for mouse development Hannon, Gregory J; Bernstein, Emily; Kim, Sang Yong ...
Nature genetics,
11/2003, Letnik:
35, Številka:
3
Journal Article
Recenzirano
To address the biological function of RNA interference (RNAi)-related pathways in mammals, we disrupted the gene Dicer1 in mice. Loss of Dicer1 lead to lethality early in development, with ...Dicer1-null embryos depleted of stem cells. Coupled with our inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggests a role for Dicer, and, by implication, the RNAi machinery, in maintaining the stem cell population during early mouse development.
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