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1.
Ecol Process ; 9(1): 22, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32391241

RESUMEN

Surface water improvements associated with the COVID-19 economic slowdown illustrate environmental resiliency and societal control over urban water quality.

2.
Data Brief ; 23: 103786, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31372433

RESUMEN

We report data on the projections of annual surface water demand and supply in the conterminous United States at a high spatial resolution from 2010s to the end of the 21st century, including: 1) water withdrawal and consumption in the water-use sectors of domestic, thermoelectric power generation, and irrigation; 2) availability of surface water generated from local watershed runoff, accumulated from upstream areas, and artificially transferred from other basins. These data were derived from the projected changes in climate, population, energy structure, technology and water uses. These data are related to the original article "Understanding the role of regional water connectivity in mitigating climate change impacts on surface water supply stress in the United States" (Duan et al., 2019) [1].

3.
Nat Commun ; 9(1): 1307, 2018 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-29636465

RESUMEN

Wildland fire impacts on surface freshwater resources have not previously been measured, nor factored into regional water management strategies. But, large wildland fires are increasing and raise concerns about fire impacts on potable water. Here we synthesize long-term records of wildland fire, climate, and river flow for 168 locations across the United States. We show that annual river flow changed in 32 locations, where more than 19% of the basin area was burned. Wildland fires enhanced annual river flow in the western regions with a warm temperate or humid continental climate. Wildland fires increased annual river flow most in the semi-arid Lower Colorado region, in spite of frequent droughts in this region. In contrast, prescribed burns in the subtropical Southeast did not significantly alter river flow. These extremely variable outcomes offer new insights into the potential role of wildfire and prescribed fire in regional water resource management, under a changing climate.

4.
Sci Total Environ ; 605-606: 376-390, 2017 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-28668749

RESUMEN

A field experiment was established in a high elevation red spruce (Picea rubens Sarg.) - balsam fir (Abies balsamea) forest on Mount Ascutney Vermont, USA in 1988 to test the nitrogen (N) saturation hypothesis, and to better understand the mechanisms causing forest decline at the time. The study established replicate control, low and high dose nitrogen addition plots (i.e., 0, 15.7 and 31.4kgNH4Cl-Nha-1yr-1). The treatments began in 1988 and continued annually until 2010, but monitoring has continued to present. During the fertilization period, forest floor C:N, net in situ N mineralization, spruce foliar Ca%, and live spruce basal area decreased with increasing N addition, while foliar spruce N% and forest floor net nitrification increased with increasing N addition. The control plots aggraded forest floor N at a rate equal to the sum of the net in situ N mineralization plus average ambient deposition. Conversely, N addition plots lost forest floor N. Following the termination of N additions in 2010, the measured tree components returned to pre-treatment levels, but forest floor processes were slower to respond. During the 30year study, site surface air temperature has increased by 0.5°C per decade, and total N deposition has decreased 5.5 to 4.0kgNha-1yr-1. There have also been three significant drought years and at least one freeze injury year after which much of the forest mortality on the N addition plots occurred. Given that there was no control for the air temperature increase, discussion of the interactive impacts of climate and change and N addition is only subjective. Predicted changes in climate, N deposition and other stressors suggest that even in the absence of N saturation, regeneration of the spruce-fir ecosystem into the next century seems unlikely despite recent region-wide growth increases.


Asunto(s)
Abies/crecimiento & desarrollo , Bosques , Nitrógeno/análisis , Picea/crecimiento & desarrollo , Cambio Climático , Nitrificación , Suelo/química , Árboles , Vermont
5.
Sci Rep ; 6: 24441, 2016 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-27100360

RESUMEN

The 170 National Forests and Grasslands (NFs) in the conterminous United States are public lands that provide important ecosystem services such as clean water and timber supply to the American people. This study investigates the potential impacts of climate change on two key ecosystem functions (i.e., water yield and ecosystem productivity) using the most recent climate projections derived from 20 Global Climate Models (GCMs) of the Coupled Model Intercomparison Project phase 5 (CMIP5). We find that future climate change may result in a significant reduction in water yield but an increase in ecosystem productivity in NFs. On average, gross ecosystem productivity is projected to increase by 76 ~ 229 g C m(-2) yr(-1) (8% ~ 24%) while water yield is projected to decrease by 18 ~ 31 mm yr(-1) (4% ~ 7%) by 2100 as a result of the combination of increased air temperature (+1.8 ~ +5.2 °C) and precipitation (+17 ~ +51 mm yr(-1)). The notable divergence in ecosystem services of water supply and carbon sequestration is expected to intensify under higher greenhouse gas emission and associated climate change in the future, posing greater challenges to managing NFs for both ecosystem services.


Asunto(s)
Cambio Climático , Ecosistema , Secuestro de Carbono , Bosques , Pradera , Lluvia , Temperatura , Estados Unidos , Abastecimiento de Agua
6.
Infect Control Hosp Epidemiol ; 33(12): 1238-41, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23143362

RESUMEN

We describe an investigation of 3 postoperative Gordonia bronchialis sternal infections. A nurse anesthetist was identified as the source of the outbreak, her scrubs likely becoming contaminated by her home washing machine. The outbreak ended after disposal of the implicated washing machine. Domestic laundering of surgical scrubs may need reevaluation.


Asunto(s)
Infecciones por Actinomycetales/transmisión , Bacteria Gordonia/aislamiento & purificación , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Enfermeras Anestesistas , Infección de la Herida Quirúrgica/microbiología , Anciano , Anciano de 80 o más Años , Vestuario , Puente de Arteria Coronaria , Mano/microbiología , Humanos , Masculino , Persona de Mediana Edad , Infección de la Herida Quirúrgica/terapia
7.
New Phytol ; 187(1): 171-183, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20406402

RESUMEN

*Hydraulic redistribution (HR) of water via roots from moist to drier portions of the soil occurs in many ecosystems, potentially influencing both water use and carbon assimilation. *By measuring soil water content, sap flow and eddy covariance, we investigated the temporal variability of HR in a loblolly pine (Pinus taeda) plantation during months of normal and below-normal precipitation, and examined its effects on tree transpiration, ecosystem water use and carbon exchange. *The occurrence of HR was explained by courses of reverse flow through roots. As the drought progressed, HR maintained soil moisture above 0.15 cm(3) cm(-3) and increased transpiration by 30-50%. HR accounted for 15-25% of measured total site water depletion seasonally, peaking at 1.05 mm d(-1). The understory species depended on water redistributed by the deep-rooted overstory pine trees for their early summer water supply. Modeling carbon flux showed that in the absence of HR, gross ecosystem productivity and net ecosystem exchange could be reduced by 750 and 400 g C m(-2) yr(-1), respectively. *Hydraulic redistribution mitigated the effects of soil drying on understory and stand evapotranspiration and had important implications for net primary productivity by maintaining this whole ecosystem as a carbon sink.


Asunto(s)
Carbono/metabolismo , Ecosistema , Pinus/fisiología , Raíces de Plantas/fisiología , Transpiración de Plantas/fisiología , Suelo , Agua/fisiología , Modelos Biológicos , Hojas de la Planta/anatomía & histología , Hojas de la Planta/fisiología , Lluvia , Estaciones del Año , Factores de Tiempo , Árboles/fisiología
8.
Environ Pollut ; 158(6): 2053-8, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20045233

RESUMEN

Federal agencies of several nations have or are currently developing guidelines for critical forest soil acid loads. These guidelines are used to establish regulations designed to maintain atmospheric acid inputs below levels shown to damage forests and streams. Traditionally, when the critical soil acid load exceeds the amount of acid that the ecosystem can absorb, it is believed to potentially impair forest health. The excess over the critical soil acid load is termed the exceedance, and the larger the exceedance, the greater the risk of ecosystem damage. This definition of critical soil acid load applies to exposure of the soil to a single, long-term pollutant (i.e., acidic deposition). However, ecosystems can be simultaneously under multiple ecosystem stresses and a single critical soil acid load level may not accurately reflect ecosystem health risk when subjected to multiple, episodic environmental stress. For example, the Appalachian Mountains of western North Carolina receive some of the highest rates of acidic deposition in the eastern United States, but these levels are considered to be below the critical acid load (CAL) that would cause forest damage. However, the area experienced a moderate three-year drought from 1999 to 2002, and in 2001 red spruce (Picea rubens Sarg.) trees in the area began to die in large numbers. The initial survey indicated that the affected trees were killed by the southern pine beetle (Dendroctonus frontalis Zimm.). This insect is not normally successful at colonizing these tree species because the trees produce large amounts of oleoresin that exclude the boring beetles. Subsequent investigations revealed that long-term acid deposition may have altered red spruce forest structure and function. There is some evidence that elevated acid deposition (particularly nitrogen) reduced tree water uptake potential, oleoresin production, and caused the trees to become more susceptible to insect colonization during the drought period. While the ecosystem was not in exceedance of the CAL, long-term nitrogen deposition pre-disposed the forest to other ecological stress. In combination, insects, drought, and nitrogen ultimately combined to cause the observed forest mortality. If any one of these factors were not present, the trees would likely not have died. This paper presents a conceptual framework of the ecosystem consequences of these interactions as well as limited plot level data to support this concept. Future assessments of the use of CAL studies need to account for multiple stress impacts to better understand ecosystem response.


Asunto(s)
Lluvia Ácida/análisis , Cambio Climático , Agricultura Forestal/métodos , Contaminantes del Suelo/análisis , Suelo/análisis , Árboles/crecimiento & desarrollo , Lluvia Ácida/toxicidad , Sequías , Ecosistema , Monitoreo del Ambiente/métodos , North Carolina , Suelo/normas , Contaminantes del Suelo/toxicidad , Temperatura , Árboles/efectos de los fármacos , Árboles/metabolismo , Agua/metabolismo
9.
Environ Manage ; 44(6): 1022-32, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19588192

RESUMEN

This study explores potential adaptation approaches in planning and management that the United States Forest Service might adopt to help achieve its goals and objectives in the face of climate change. Availability of information, vulnerability of ecological and socio-economic systems, and uncertainties associated with climate change, as well as the interacting non-climatic changes, influence selection of the adaptation approach. Resource assessments are opportunities to develop strategic information that could be used to identify and link adaptation strategies across planning levels. Within a National Forest, planning must incorporate the opportunity to identify vulnerabilities to climate change as well as incorporate approaches that allow management adjustments as the effects of climate change become apparent. The nature of environmental variability, the inevitability of novelty and surprise, and the range of management objectives and situations across the National Forest System implies that no single approach will fit all situations. A toolbox of management options would include practices focused on forestalling climate change effects by building resistance and resilience into current ecosystems, and on managing for change by enabling plants, animals, and ecosystems to adapt to climate change. Better and more widespread implementation of already known practices that reduce the impact of existing stressors represents an important "no regrets" strategy. These management opportunities will require agency consideration of its adaptive capacity, and ways to overcome potential barriers to these adaptation options.


Asunto(s)
Cambio Climático , Agricultura Forestal , Estados Unidos
10.
Blood Cells Mol Dis ; 43(2): 141-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19409822

RESUMEN

One of the most commonly inherited anemias in man is Hereditary Spherocytosis (HS) with an incidence of 1 in 2000 for persons of Northern European descent. Mouse models of HS include spontaneous inherited hemolytic anemias and those generated by gene targeting. The Neonatal anemia (Nan) mouse is a novel model of HS generated by N-ethyl-N-nitrosurea mutagenesis and suffers from a severe neonatal anemia. Adult Nan mice have a lifelong hemolytic anemia with decreased red blood cell numbers, hematocrit, and hemoglobin, but elevated zinc protoporphyrin levels. Blood smears taken from Nan mice show a hypochromic anemia characterized by poikilocytosis, anisocytosis and polychromasia. The Nan phenotype can be transferred by bone marrow transplantation indicating that the defect is intrinsic to bone marrow. The hemolytic anemia in adult Nan mice can be identified by osmotic fragility testing. Examination of the erythrocyte membrane skeleton proteins (EMS) reveals a global deficiency of these proteins with protein 4.1a being completely absent. The Nan locus maps to mouse Chromosome 8 and does not co-localize with any known EMS genes. The identification of the Nan gene will likely uncover a novel protein that contributes to the stability of the EMS and may identify a new mutation for HS.


Asunto(s)
Anemia Hemolítica/metabolismo , Cromosomas de los Mamíferos/genética , Membrana Eritrocítica/metabolismo , Eritrocitos/metabolismo , Proteínas de la Membrana/metabolismo , Anemia Hemolítica/genética , Anemia Hemolítica/patología , Animales , Trasplante de Médula Ósea , Mapeo Cromosómico , Modelos Animales de Enfermedad , Membrana Eritrocítica/patología , Eritrocitos/patología , Eritrocitos/ultraestructura , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Rastreo
11.
Plant Cell Environ ; 32(8): 980-91, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19344336

RESUMEN

The study examined the relationships between whole tree hydraulic conductance (K(tree)) and the conductance in roots (K(root)) and leaves (K(leaf)) in loblolly pine trees. In addition, the role of seasonal variations in K(root) and K(leaf) in mediating stomatal control of transpiration and its response to vapour pressure deficit (D) as soil-dried was studied. Compared to trunk and branches, roots and leaves had the highest loss of conductivity and contributed to more than 75% of the total tree hydraulic resistance. Drought altered the partitioning of the resistance between roots and leaves. As soil moisture dropped below 50%, relative extractable water (REW), K(root) declined faster than K(leaf). Although K(tree) depended on soil moisture, its dynamics was tempered by the elongation of current-year needles that significantly increased K(leaf) when REW was below 50%. After accounting for the effect of D on g(s), the seasonal decline in K(tree) caused a 35% decrease in g(s) and in its sensitivity to D, responses that were mainly driven by K(leaf) under high REW and by K(root) under low REW. We conclude that not only water stress but also leaf phenology affects the coordination between K(tree) and g(s) and the acclimation of trees to changing environmental conditions.


Asunto(s)
Pinus taeda/fisiología , Hojas de la Planta/fisiología , Raíces de Plantas/fisiología , Estomas de Plantas/fisiología , Transpiración de Plantas/fisiología , Estaciones del Año , Suelo/análisis , Presión de Vapor , Agua/metabolismo
12.
Environ Pollut ; 149(3): 281-92, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17629382

RESUMEN

Concern regarding the impacts of continued nitrogen and sulfur deposition on ecosystem health has prompted the development of critical acid load assessments for forest soils. A critical acid load is a quantitative estimate of exposure to one or more pollutants at or above which harmful acidification-related effects on sensitive elements of the environment occur. A pollutant load in excess of a critical acid load is termed exceedance. This study combined a simple mass balance equation with national-scale databases to estimate critical acid load and exceedance for forest soils at a 1-km(2) spatial resolution across the conterminous US. This study estimated that about 15% of US forest soils are in exceedance of their critical acid load by more than 250eqha(-1)yr(-1), including much of New England and West Virginia. Very few areas of exceedance were predicted in the western US.


Asunto(s)
Ácidos/análisis , Ecología/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/análisis , Árboles , Lluvia Ácida , Adsorción , Bases de Datos Factuales , Ecología/métodos , Humanos , Nitrógeno/análisis , Suelo/análisis , Contaminantes del Suelo/análisis , Azufre/análisis , Estados Unidos
13.
Environ Pollut ; 149(3): 293-302, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17643595

RESUMEN

Recent studies have demonstrated that natural abundance (15)N can be a useful tool for assessing nitrogen saturation, because as nitrification and nitrate loss increase, delta(15)N of foliage and soil also increases. We measured foliar delta(15)N at 11 high-elevation spruce-fir stands along an N deposition gradient in 1987-1988 and at seven paired northern hardwood and spruce-fir stands in 1999. In 1999, foliar delta(15)N increased from -5.2 to -0.7 per thousand with increasing N deposition from Maine to NY. Foliar delta(15)N decreased between 1987-1988 and 1999, while foliar %N increased and foliar C:N decreased at most sites. Foliar delta(15)N was strongly correlated with N deposition, and was also positively correlated with net nitrification potential and negatively correlated with soil C:N ratio. Although the increase in foliar %N is consistent with a progression towards N saturation, other results of this study suggest that, in 1999, these stands were further from N saturation than in 1987-1988.


Asunto(s)
Contaminantes Ambientales/análisis , Nitrógeno/análisis , Hojas de la Planta/química , Árboles/crecimiento & desarrollo , Región de los Apalaches , Clima , Monitoreo del Ambiente/métodos , Humanos , New England , Isótopos de Nitrógeno/análisis , Picea/crecimiento & desarrollo , Hojas de la Planta/crecimiento & desarrollo , Suelo/análisis , Tiempo
14.
Environ Pollut ; 149(3): 315-26, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17597271

RESUMEN

Simple mass balance equations (SMBE) of critical acid loads (CAL) in forest soil were developed to assess potential risks of air pollutants to ecosystems. However, to apply SMBE reliably at large scales, SMBE must be tested for adequacy and uncertainty. Our goal was to provide a detailed analysis of uncertainty in SMBE so that sound strategies for scaling up CAL estimates to the national scale could be developed. Specifically, we wanted to quantify CAL uncertainty under natural variability in 17 model parameters, and determine their relative contributions in predicting CAL. Results indicated that uncertainty in CAL came primarily from components of base cation weathering (BC(w); 49%) and acid neutralizing capacity (46%), whereas the most critical parameters were BC(w) base rate (62%), soil depth (20%), and soil temperature (11%). Thus, improvements in estimates of these factors are crucial to reducing uncertainty and successfully scaling up SMBE for national assessments of CAL.


Asunto(s)
Contaminación del Aire/estadística & datos numéricos , Biomasa , Ecosistema , Modelos Teóricos , Ácidos/análisis , Contaminación del Aire/efectos adversos , Biodegradación Ambiental , Clima , Monitoreo del Ambiente/métodos , Suelo/análisis , Contaminantes del Suelo/análisis , Incertidumbre
15.
Environ Pollut ; 149(3): 303-14, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17600603

RESUMEN

We evaluated foliar and forest floor chemistry across a gradient of N deposition in the Northeast at 11 red spruce (Picea rubens Sarg.) sites in 1987/1988 and foliar and forest floor chemistry and basal area growth at six paired spruce and deciduous sites in 1999. The six red spruce plots were a subset of the original 1987/1988 spruce sites. In 1999, we observed a significant correlation between mean growing season temperature and red spruce basal area growth. Red spruce and deciduous foliar %N correlated significantly with N deposition. Although N deposition has not changed significantly from 1987/1988 to 1999, net nitrification potential decreased significantly at Whiteface. This decrease in net potential nitrification is not consistent with the N saturation hypothesis and suggests that non-N deposition controls, such as climatic factors and immobilization of down dead wood, might have limited N cycling.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Monitoreo del Ambiente/métodos , Nitrógeno/efectos adversos , Hojas de la Planta/crecimiento & desarrollo , Árboles/crecimiento & desarrollo , Acer/crecimiento & desarrollo , Región de los Apalaches , New England , Pinus/crecimiento & desarrollo , Tiempo
16.
Am J Med Genet A ; 143A(5): 422-9, 2007 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-17036336

RESUMEN

Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes in the 15q11-q13 region. To further characterize alterations in gene expression in this classical obesity syndrome we used whole genome microarrays to study a PWS mouse model resulting from a paternally derived imprinting center (IC) deletion (PWS IC deletion). These mice die generally within 2-3 days of life (reflective of failure to thrive in infants with PWS) and therefore, the analysis was performed on RNA extracted from the whole brain of PWS IC deletion mice and normal littermates at less than 24 hr after birth. Of more than 45,000 probes examined, 26,471 (59%) were detected for further analysis, and 69 had a significant change in expression of at least 1.5-fold and a false discovery rate (FDR) of 5%. Eight of the genes with differential expression were imprinted and from the PWS critical region (PWSCR). The three genes with the highest expression in the PWS IC mice were pro-opiomelanocortin (Pomc) and two transcripts of unknown function. Pomc knockout mice have been shown to develop obesity. Therefore, elevated Pomc RNA in PWS IC deletion neonatal mice may be an important genetic factor in the survival of these mice as it may affect eating behavior. Interestingly, Mc5r, a melanocortin receptor known to directly respond to Pomc expression changes, was upregulated as well. Mc5r is known to be involved with thermoregulation which is reportedly abnormal in PWS infants. These observations support a role for Pomc and the network of genes involved in regulating energy homeostasis in the early clinical findings of failure to thrive observed in PWS. Other notable patterns include three previously unstudied transcripts that are expressed only from the paternal allele under regulatory control of the IC and include AK013560, BB3144814, and BB182944 (whose genes are located in the mouse PWSCR on chromosome 7B). As expected, all the known paternally expressed genes from the PWSCR had detection signals below the threshold in the PWS IC deletion mice but were clearly detectable in control littermates. Several of the genes in this study were further examined by quantitative reverse transcription-PCR (RT-PCR) to confirm their expression status. Further analysis of gene expression in these mice may lead to novel pathways affected in PWS. These results, along with other recent reports, suggest that the cumulative effect of modest changes in expression of many genes, especially genes involved in energy metabolism, contribute to the failure to thrive of infants with PWS.


Asunto(s)
Modelos Animales de Enfermedad , Eliminación de Gen , Impresión Genómica/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Síndrome de Prader-Willi/genética , Animales , Animales Recién Nacidos , Autoantígenos/genética , Cromosomas de los Mamíferos , Femenino , Genoma , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ribonucleoproteínas Nucleares Pequeñas/genética , Proteínas Nucleares snRNP
17.
Neuromuscul Disord ; 16(3): 192-203, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16487708

RESUMEN

Duchenne muscular dystrophy is a progressive muscle disease characterized by increasing muscle weakness and death by the third decade. mdx mice exhibit the underlying muscle disease but appear physically normal with ordinary lifespans, possibly due to compensatory expression of utrophin. In contrast, double mutant mice (mdx/utrn(-/-)), deficient for both dystrophin and utrophin die by approximately 3 months and suffer from severe muscle weakness, growth retardation, and severe spinal curvature. The capacity of human retinal dystrophin (Dp260) to compensate for the missing 427 kDa muscle dystrophin was tested in mdx/utrn(-/-) mice. Functional outcomes were assessed by histology, EMG, MRI, mobility, weight and longevity. MCK-driven transgenic expression of Dp260 in mdx/utrn(-/-) mice converts their disease course from a severe, lethal muscular dystrophy to a viable, mild myopathic phenotype. This finding is relevant to the design of exon-skipping therapeutic strategies since Dp260 lacks dystrophin exons 1-29.


Asunto(s)
Distrofina/genética , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Distrofia Muscular Animal/terapia , Transgenes , Factores de Edad , Animales , Western Blotting/métodos , Distrofina/deficiencia , Electromiografía/métodos , Expresión Génica/fisiología , Terapia Genética , Humanos , Inmunohistoquímica/métodos , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos mdx , Ratones Transgénicos , Necrosis , Tomografía Computarizada por Rayos X/métodos , Utrofina/genética
18.
Genomics ; 86(6): 668-73, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16289749

RESUMEN

Defects in iron absorption and utilization lead to iron deficiency and anemia. While iron transport by transferrin receptor-mediated endocytosis is well understood, it is not completely clear how iron is transported from the endosome to the mitochondria where heme is synthesized. We undertook a positional cloning project to identify the causative mutation for the hemoglobin-deficit (hbd) mouse mutant, which suffers from a microcytic, hypochromic anemia apparently due to defective iron transport in the endocytosis cycle. As shown by previous studies, reticulocyte iron accumulation in homozygous hbd/hbd mice is deficient despite normal binding of transferrin to its receptor and normal transferrin uptake in the cell. We have identified a strong candidate gene for hbd, Sec15l1, a homologue to yeast SEC15, which encodes a key protein in vesicle docking. The hbd mice have an exon deletion in Sec15l1, which is the first known mutation of a SEC gene homologue in mammals.


Asunto(s)
Anemia Ferropénica/genética , Endocitosis/genética , Exones/genética , Expresión Génica , Hierro/metabolismo , Proteínas de la Membrana/genética , Eliminación de Secuencia/genética , Animales , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Análisis Mutacional de ADN , Proteínas de la Membrana/metabolismo , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Vesículas Transportadoras/metabolismo
19.
Genomics ; 85(3): 330-7, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15718100

RESUMEN

Genes playing essential roles in iron homeostasis have yet to be identified. We report the discovery of a strong candidate gene affecting iron homeostasis in two allelic anemia mouse mutants: hea (hereditary erythroblastic anemia) and fsn (flaky skin). To clone this novel gene positionally, we established a large backcross, which generated a critical region of seven genes from which only one gene exhibited a mutation in hea mice. This was a deletion in Ttc7 (tetratricopeptide repeat domain 7) extending from exon 1 to exon 14. Correspondingly, the allelic variant fsn mice showed a mutation of an ETn retrotransposon integration into intron 14 of the Ttc7 gene, which results in an abnormal Ttc7 RNA transcript. TTC7 is a member of the TPR repeat protein family known to interact with other proteins, to facilitate transport, and to act as chaperone or scaffolding proteins. We speculate that TTC7 plays an important role in iron transport.


Asunto(s)
Anemia/genética , Clonación Molecular , Homeostasis/genética , Hierro/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN , Elementos Transponibles de ADN , Ratones , Datos de Secuencia Molecular , Mutación , Eliminación de Secuencia , Homología de Secuencia de Aminoácido
20.
Blood ; 104(5): 1511-8, 2004 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-15155459

RESUMEN

Understanding iron metabolism has been enhanced by identification of genes for iron deficiency mouse mutants. We characterized the genetics and iron metabolism of the severe anemia mutant hea (hereditary erythroblastic anemia), which is lethal at 5 to 7 days. The hea mutation results in reduced red blood cell number, hematocrit, and hemoglobin. The hea mice also have elevated Zn protoporphyrin and serum iron. Blood smears from hea mice are abnormal with elevated numbers of smudge cells. Aspects of the hea anemia can be transferred by hematopoietic stem cell transplantation. Neonatal hea mice show a similar hematologic phenotype to the flaky skin (fsn) mutant. We mapped the hea gene near the fsn locus on mouse chromosome 17 and show that the mutants are allelic. Both tissue iron overloading and elevated serum iron are also found in hea and fsn neonates. There is a shift from iron overloading to iron deficiency as fsn mice age. The fsn anemia is cured by an iron-supplemented diet, suggesting an iron utilization defect. When this diet is removed there is reversion to anemia with concomitant loss of overloaded iron stores. We speculate that the hea/fsn gene is required for iron uptake into erythropoietic cells and for kidney iron reabsorption.


Asunto(s)
Hierro de la Dieta/farmacocinética , Talasemia beta/genética , Talasemia beta/metabolismo , Animales , Animales Recién Nacidos , Mapeo Cromosómico , Cromosomas de los Mamíferos , Trasplante de Tejido Fetal , Trasplante de Células Madre Hematopoyéticas , Hierro de la Dieta/sangre , Hígado/citología , Hígado/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Mutantes , Fenotipo , Talasemia beta/dietoterapia
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