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1.
Bull Math Biol ; 83(5): 46, 2021 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-33745017

RESUMEN

The distribution and use of pathogen-free planting material ("clean seeds") is a promising method to control plant diseases in developing countries. We address the question of minimizing disease prevalence in plants through the optimal usage of clean seeds. We consider the simplest possible S-I model together with a simple economic criterion to be maximized. The static optimization problem shows a diversity of possible outcomes depending on economical and epidemiological parameters. We derive a simple condition showing to what extent subsidizing clean seeds relative to the epidemiological features of the disease may help eradicate or control the disease. Then we consider dynamic optimal control and Pontryagin's maximum principle to study the optimal usage of clean seeds to control the disease. The dynamical results are comparable to the static ones and are even simpler in some sense. In particular, the condition on the critical subsidy rate that makes clean seed usage economically viable is unchanged from the static optimization case. We discuss how these results may apply to the control of maize lethal necrosis in East-Africa.


Asunto(s)
Modelos Biológicos , Enfermedades de las Plantas , Virus de Plantas , Semillas , África Oriental , Enfermedades de las Plantas/prevención & control , Virus de Plantas/fisiología , Semillas/virología , Organismos Libres de Patógenos Específicos , Zea mays/virología
2.
Hum Mol Genet ; 24(14): 4147-57, 2015 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-25935003

RESUMEN

Genome-wide association studies in Crohn's disease (CD) have identified 140 genome-wide significant loci. However, identification of genes driving association signals remains challenging. Furthermore, genome-wide significant thresholds limit false positives at the expense of decreased sensitivity. In this study, we explored gene features contributing to CD pathogenicity, including gene-based association data from CD and autoimmune (AI) diseases, as well as gene expression features (eQTLs, epigenetic markers of expression and intestinal gene expression data). We developed an integrative model based on a CD reference gene set. This integrative approach outperformed gene-based association signals alone in identifying CD-related genes based on statistical validation, gene ontology enrichment, differential expression between M1 and M2 macrophages and a validation using genes causing monogenic forms of inflammatory bowel disease as a reference. Besides gene-level CD association P-values, association with AI diseases was the strongest predictor, highlighting generalized mechanisms of inflammation, and the interferon-γ pathway particularly. Within the 140 high-confidence CD regions, 598 of 1328 genes had low prioritization scores, highlighting genes unlikely to contribute to CD pathogenesis. For select regions, comparably high integrative model scores were observed for multiple genes. This is particularly evident for regions having extensive linkage disequilibrium such as the IBD5 locus. Our analyses provide a standardized reference for prioritizing potential CD-related genes, in regions with both highly significant and nominally significant gene-level association P-values. Our integrative model may be particularly valuable in prioritizing rare, potentially private, missense variants for which genome-wide evidence for association may be unattainable.


Asunto(s)
Enfermedad de Crohn/genética , Expresión Génica , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Interferón gamma/metabolismo , Intestinos , Desequilibrio de Ligamiento , Modelos Logísticos , Macrófagos , Análisis por Micromatrices , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ARN
3.
Int J Obes (Lond) ; 2017 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-29087390

RESUMEN

BACKGROUND/OBJECTIVES: To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone. SUBJECTS/METHODS: Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment. RESULTS: mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ~55% and ~4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone. CONCLUSIONS: Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.192.

4.
Ir Med J ; 110(10): 655, 2017 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-29465845

RESUMEN

Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway narrowing occurring after exercise which may impact athletic performance. Studies report 10% of the general population and up to 90% of asthmatics experience EIB. Ninety-two players from three elite hurling squads underwent a spirometric field-based provocation test with real-time heart rate monitoring and lactate measurements to ensure adequate exertion. Players with a new diagnosis of EIB and those with a negative field-test but with a previous label of EIB or asthma underwent further reversibility testing and if negative, methacholine challenge. Eight (8.7%) of players had EIB, with one further athlete having asthma with a negative field test. Interestingly, only three out of 12 players who had previously been physician-labelled with EIB or asthma had their diagnosis objectively confirmed. Our study highlights the role of objective testing in EIB.


Asunto(s)
Asma/complicaciones , Rendimiento Atlético , Enfermedades Bronquiales/etiología , Deportes , Asma/diagnóstico , Asma Inducida por Ejercicio/complicaciones , Asma Inducida por Ejercicio/diagnóstico , Enfermedades Bronquiales/diagnóstico , Enfermedades Bronquiales/epidemiología , Pruebas de Provocación Bronquial , Constricción Patológica/epidemiología , Constricción Patológica/etiología , Humanos , Prevalencia
5.
J Asthma ; 51(4): 440-5, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24393080

RESUMEN

OBJECTIVES: The aim of this study was to evaluate inhaler technique and symptom control in patients with poorly controlled asthma at baseline and at follow-up in a dedicated asthma clinic in a tertiary hospital. We also investigated the impact of asthma on these patients' quality of life. METHODS: Patients referred to a newly established asthma clinic in Cork University Hospital were prospectively recruited over a 6-month period. Their inhaler technique was assessed by a pulmonary nurse specialist using a validated scoring system. They received instruction on inhaler usage when scores were suboptimal. Patients completed a validated asthma control questionnaire (ACQ) and asthma quality of life questionnaire (AQLQ). At follow-up 3-4 months later, the inhaler technique was reassessed and the ACQ questionnaire repeated. RESULTS: Forty-six patients were recruited (female = 74%), and 40/46 were followed up. Mean [SD] FEV1 % predicted at baseline = 76.5% [21.5]. About 63% of the patients were classified as incorrectly using their inhaler at their initial assessment. This decreased to 20% at follow-up, indicating an overall significant improvement in inhaler usage post-training (p = 0.003). ACQ scores improved significantly from median [interquartile range] 2.70 [1.66] to 2.00 [1.90] (p = 0.002). Baseline measurement indicated that patients' quality of life was moderately affected by asthma, with a median AQLQ score of 4.75 [1.97]. CONCLUSION: This study demonstrates the importance of educating and formally assessing inhaler technique in patients with asthma as a part of their ongoing clinical review.


Asunto(s)
Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Nebulizadores y Vaporizadores/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Educación del Paciente como Asunto/métodos , Administración por Inhalación , Adulto , Atención Ambulatoria/métodos , Instituciones de Atención Ambulatoria , Asma/diagnóstico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Control de Calidad , Medición de Riesgo , Resultado del Tratamiento , Adulto Joven
6.
Mol Ecol ; 21(17): 4171-89, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22574714

RESUMEN

The field of molecular ecology has burgeoned into a large discipline spurred on by technical innovations that facilitate the rapid acquisition of large amounts of genotypic data, by the continuing development of theory to interpret results, and by the availability of computer programs to analyse data sets. As the discipline grows, however, misconceptions have become enshrined in the literature and are perpetuated by routine citations to other articles in molecular ecology. These misconceptions hamper a better understanding of the processes that influence genetic variation in natural populations and sometimes lead to erroneous conclusions. Here, we consider eight misconceptions commonly appearing in the literature: (i) some molecular markers are inherently better than other markers; (ii) mtDNA produces higher F(ST) values than nDNA; (iii) estimated population coalescences are real; (iv) more data are always better; (v) one needs to do a Bayesian analysis; (vi) selective sweeps influence mtDNA data; (vii) equilibrium conditions are critical for estimating population parameters; and (viii) having better technology makes us smarter than our predecessors. This is clearly not an exhaustive list and many others can be added. It is, however, sufficient to illustrate why we all need to be more critical of our own understanding of molecular ecology and to be suspicious of self-evident truths.


Asunto(s)
Ecología/métodos , Genética de Población/métodos , Biología Molecular/métodos , Animales , Teorema de Bayes , Núcleo Celular/genética , Biología Computacional , ADN Mitocondrial/genética , Evolución Molecular , Marcadores Genéticos , Repeticiones de Microsatélite , Modelos Genéticos
7.
Sustain Sci ; 17(3): 1059-1076, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35261685

RESUMEN

Hydrological systems are important to society as water resources and effective management requires an understanding of how water and humans influence each other. To describe human-water connections it is necessary to bridge social and natural sciences. To this end, we construct an interdisciplinary graphical framework for evaluating potential human-water system resilience, which is a tool to show the spatial and temporal response to system change of both human and natural systems. This helps to identify the ways that human responses to change relate to changing water resources and identifies important thresholds and potential disconnects that would create vulnerability. We further use this tool to describe a dynamic, coupled human-water system present in the arid Sierra de la Giganta region of Baja California Sur, Mexico. In this remote mountain range, there is a community (self-identifying as Choyeros) who rely on spring water for ranching and subsistence. Using mixed methods of hydrogeochemistry and anthropology, we describe spatial connectivity and temporal changes of both hydrologic and social systems. We use these observations to examine the Choyero response to system changes and explore the topology of the various approaches that the community employs to adapt to changing water availability. The framework guides dialogue to constrain the types of policies, strategies, and responses that help to promote the sustainability of water resources. This framework can be used to compare systems across spatio-temporal scales to produce more generalizable and communicable insights of coupled human-natural systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01101-6.

8.
Front Neurol ; 12: 663911, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025568

RESUMEN

Background: Spinal muscular atrophy (SMA) linked to chromosome 5q is an inherited progressive neuromuscular disorder with a narrow therapeutic window for optimal treatment. Although genetic testing provides a definitive molecular diagnosis that can facilitate access to effective treatments, limited awareness and other barriers may prohibit widespread testing. In this study, the clinical and molecular findings of SMA Identified-a no-charge sponsored next-generation sequencing (NGS)-based genetic testing program for SMA diagnosis-are reported. Methods: Between March 2018 and March 2020, unrelated individuals who had a confirmed or suspected SMA diagnosis or had a family history of SMA were eligible. All individuals underwent diagnostic genetic testing for SMA at clinician discretion. In total, 2,459 individuals were tested and included in this analysis. An NGS-based approach interrogated sequence and copy number of SMN1 and SMN2. Variants were confirmed by multiplex ligation-dependent probe amplification sequencing. Individuals were categorized according to genetic test results: diagnostic (two pathogenic SMN1 variants), nearly diagnostic (SMN1 exon-7 deletion with a variant of uncertain significance [VUS] in SMN1 or SMN2), indeterminate VUS (one VUS in SMN1 or SMN2), carrier (heterozygous SMN1 deletion only), or negative (no pathogenic variants or VUS in SMN1 or SMN2). Diagnostic yield was calculated. Genetic test results were analyzed based on clinician-reported clinical features and genetic modifiers (SMN2 copy number and SMN2 c.859G>C). Results: In total, 2,459 unrelated individuals (mean age 24.3 ± 23.0 years) underwent diagnostic testing. The diagnostic yield for diagnostic plus nearly diagnostic results was 31.3% (n = 771/2,459). Age of onset and clinical presentation varied considerably for individuals and was dependent on SMN2 copy number. Homozygous deletions represented the most common genetic etiology (96.2%), with sequence variants also observed in probands with clinical diagnoses of SMA. Conclusions: Using a high-yield panel test in a no-charge sponsored program early in the diagnostic odyssey may open the door for medical interventions in a substantial number of individuals with SMA. These findings have potential implications for clinical management of probands and their families.

9.
Diabetologia ; 53(3): 541-51, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20012595

RESUMEN

AIMS/HYPOTHESIS: Insulin resistance in skeletal muscle is linked to mitochondrial dysfunction in obesity and type 2 diabetes. Emerging evidence indicates that reversible phosphorylation regulates oxidative phosphorylation (OxPhos) proteins. The aim of this study was to identify and quantify site-specific phosphorylation of the catalytic beta subunit of ATP synthase (ATPsyn-beta) and determine protein abundance of ATPsyn-beta and other OxPhos components in skeletal muscle from healthy and insulin-resistant individuals. METHODS: Skeletal muscle biopsies were obtained from lean, healthy, obese, non-diabetic and type 2 diabetic volunteers (each group n = 10) for immunoblotting of proteins, and hypothesis-driven identification and quantification of phosphorylation sites on ATPsyn-beta using targeted nanospray tandem mass spectrometry. Volunteers were metabolically characterised by euglycaemic-hyperinsulinaemic clamps. RESULTS: Seven phosphorylation sites were identified on ATPsyn-beta purified from human skeletal muscle. Obese individuals with and without type 2 diabetes were characterised by impaired insulin-stimulated glucose disposal rates, and showed a approximately 30% higher phosphorylation of ATPsyn-beta at Tyr361 and Thr213 (within the nucleotide-binding region of ATP synthase) as well as a coordinated downregulation of ATPsyn-beta protein and other OxPhos components. Insulin increased Tyr361 phosphorylation of ATPsyn-beta by approximately 50% in lean and healthy, but not insulin-resistant, individuals. CONCLUSIONS/INTERPRETATION: These data demonstrate that ATPsyn-beta is phosphorylated at multiple sites in human skeletal muscle, and suggest that abnormal site-specific phosphorylation of ATPsyn-beta together with reduced content of OxPhos proteins contributes to mitochondrial dysfunction in insulin resistance. Further characterisation of phosphorylation of ATPsyn-beta may offer novel targets of treatment in human diseases with mitochondrial dysfunction, such as diabetes.


Asunto(s)
Resistencia a la Insulina , ATPasas de Translocación de Protón Mitocondriales/química , Músculos/metabolismo , Adulto , Sitios de Unión , Catálisis , Estudios de Cohortes , Femenino , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Fosforilación , Tirosina/química
10.
J Cell Biol ; 109(1): 421-7, 1989 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2663882

RESUMEN

Lymphocyte trafficking is a fundamental aspect of the immune system that allows B and T lymphocytes with diverse antigen recognition specificities to be exposed to various antigenic stimuli in spatially distinct regions of an organism. A lymphocyte adhesion molecule that is involved with this trafficking phenomenon has been termed the homing receptor. Previous work (Lasky, L., T. Yednock, M. Singer, D. Dowbenko, C. Fennie, H. Rodriguez, T. Nguyen, S. Stachel, and S. Rosen. 1989. Cell. 56:1045-1055) has characterized a cDNA clone encoding a murine homing receptor that is involved in trafficking of lymphocytes to peripheral lymph nodes. This molecule was found to contain a number of protein motifs, the most intriguing of which was a carbohydrate binding domain, or lectin, that is apparently involved in the adhesive interaction between murine lymphocytes and peripheral lymph node endothelium. In this study, we have used the murine cDNA clone to isolate a human homologue of this peripheral lymph node-specific adhesion molecule. The human receptor was found to be highly homologous to the murine receptor in overall sequence, but showed no sequence similarity to another surface protein that may be involved with human lymphocyte homing, the Hermes glycoprotein. The extracellular region of the human receptor contained an NH2 terminally located carbohydrate binding domain followed by an EGF-like domain and a domain containing two repeats of a complement binding motif. Transient cell transfection assays using the human receptor cDNA showed that it encoded a surface glycoprotein that cross reacted with a polyclonal antibody directed against the murine peripheral lymph node homing receptor. Interestingly, the human receptor showed a high degree of sequence homology to another human cell adhesion glycoprotein, the endothelial cell adhesion molecule ELAM.


Asunto(s)
Adhesión Celular , Glicoproteínas de Membrana/fisiología , Receptores Inmunológicos/fisiología , Secuencia de Aminoácidos , Antígenos de Superficie/fisiología , Secuencia de Bases , Moléculas de Adhesión Celular , Clonación Molecular , ADN/genética , Humanos , Lectinas , Glicoproteínas de Membrana/ultraestructura , Datos de Secuencia Molecular , Receptores Inmunológicos/ultraestructura , Receptores Mensajeros de Linfocitos , Relación Estructura-Actividad
11.
J Cell Biol ; 110(1): 147-53, 1990 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1688560

RESUMEN

Murine and human leukocytes express surface glycoproteins, termed homing receptors (HRs), containing lectin-like, EGF-like (egf), and complement binding-like domains, that apparently endow these cells with the ability to home to peripheral lymph nodes (pln's) by virtue of an adhesive interaction with the pln postcapillary venule endothelium. The murine pln HR was initially characterized with a rat monoclonal antibody, Mel 14, that was specific for the murine form of the receptor. This work demonstrated that Mel 14 blocked the binding of murine lymphocytes to pln endothelium both in vitro and in vivo, a result consistent with the possibility that this monoclonal antibody recognizes a region of the HR that is involved with endothelium recognition and adhesion. In addition, this antibody also blocked the binding to the HR of PPME, a polyphosphomannan carbohydrate known to inhibit lymphocyte-pln endothelium interactions, suggesting that Mel 14 may recognize the lectin domain of the pln HR. Here we show that, while Mel 14 recognized truncated HR containing both the lectin and egf domains, antibody recognition was lost when the lectin domain alone was expressed. Chimeric molecules, in which regions of the lectin domain of the non-Mel 14-reactive human pln HR were replaced with homologous regions of the murine pln HR, demonstrated that the Mel 14 recognition site is within the NH2-terminal 53 amino acids of the lectin domain. These results suggest that the Mel 14 monoclonal antibody recognizes a determinant within the lectin domain of the pln HR whose conformation may be dependent upon the presence of the egf domain. Since Mel 14 efficiently blocks lymphocyte-endothelial interactions, these results support the hypothesis that the pln HR lectin domain may be directly involved with binding of lymphocytes to a carbohydrate ligand on the pln postcapillary venule endothelium.


Asunto(s)
Anticuerpos Monoclonales , Antígenos de Superficie/análisis , Epítopos/análisis , Lectinas/análisis , Ganglios Linfáticos/inmunología , Glicoproteínas de Membrana/análisis , Receptores Inmunológicos/análisis , Animales , Complejo Antígeno-Anticuerpo , Quimera , Deleción Cromosómica , Humanos , Inmunoglobulina G , Mananos , Manosafosfatos , Ratones , Mutación , Lectinas de Plantas , Conformación Proteica , Receptores Inmunológicos/genética , Receptores Inmunológicos/inmunología , Receptores Mensajeros de Linfocitos , Proteínas Recombinantes/análisis , Transfección
12.
Science ; 248(4956): 724-7, 1990 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-2333522

RESUMEN

Female green turtles exhibit strong nest-site fidelity as adults, but whether the nesting beach is the natal site is not known. Under the natal homing hypothesis, females return to their natal beach to nest, whereas under the social facilitation model, virgin females follow experienced breeders to nesting beaches and after a "favorable" nesting experience, fix on that site for future nestings. Differences shown in mitochondrial DNA genotype frequency among green turtle colonies in the Caribbean Sea and Atlantic Ocean are consistent with natal homing expectations and indicate that social facilitation to nonnatal sites is rare.


Asunto(s)
ADN Mitocondrial/genética , Orientación , Facilitación Social , Tortugas/fisiología , Animales , Femenino , Genotipo , Modelos Psicológicos , Tortugas/genética
13.
Science ; 247(4941): 449-50, 1990 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-17788612

RESUMEN

The temporal and spatial patterns of anthocyanin pigmentation in the maize plant are determined by the presence or absence of the R protein product, a presumed transcriptional activator. At least 50 unique patterns of pigmentation, conditioned by members of the R gene family, have been described. In this study, microprojectiles were used to introduce into maize cells a vector containing the transcription unit from one of these genes (Lc) fused to a constitutive promoter. This chimeric gene induces cell autonomous pigmentation in tissues that are not normally pigmented by the Lc gene. As a reporter for gene expression studies in maize, R is unique because it can be quantified in living tissue simply by counting the number of pigmented cells following bombardment. R may also be useful as a visible marker for selecting stably transformed cell lineages that can give rise to transgenic plants.

14.
Science ; 247(4939): 212-4, 1990 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-1688472

RESUMEN

The first intron of the RNA for the acetylcholine receptor (AChR) alpha subunit shows a ringlike distribution around nuclei in multinucleated myotubes by in situ hybridization. This pattern is not observed for an actin intron or U1 RNA. Quantitation of the intron sequences reveals large variations in the amount of both the AChR and actin introns between nuclei within the same myotube, although all nuclei express equivalent amounts of U1 RNA. This differential RNA expression indicates that nuclei can individually control expression of messenger RNAs. The restricted distribution of the AChR intron RNA suggests a previously unknown step in RNA processing.


Asunto(s)
Intrones , Músculos/ultraestructura , Membrana Nuclear/análisis , ARN/análisis , Receptores Colinérgicos/genética , Actinas/genética , Animales , Embrión de Pollo , Expresión Génica , Hibridación de Ácido Nucleico , ARN/genética , Sondas ARN , ARN Mensajero/genética , Ribonucleoproteínas/genética , Ribonucleoproteínas Nucleares Pequeñas
16.
Mol Ecol ; 17(24): 5336-48, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19121001

RESUMEN

Seascapes are complex environments, and populations are often isolated by factors other than distance. Here we investigate the role of coastal habitat preference and philopatry in shaping the distribution and population structure of lemon sharks. The genus Negaprion comprises the amphiatlantic lemon shark (N. brevirostris), with a relict population in the eastern Pacific, and its Indo-West Pacific sister species, the sicklefin lemon shark (N. acutidens). Analyzing 138 individuals throughout the range of N. brevirostris (N = 80) and N. acutidens (N = 58) at microsatellite loci (nine and six loci, respectively) and the mitochondrial control region, we find evidence of allopatric speciation corresponding to the Tethys Sea closure (10-14 million years ago) and isolation of the eastern Pacific N. brevirostris population via the emergence of the Isthmus of Panama (approximately 3.5 million years ago). There is significant isolation by oceanic distance (R(2) = 0.89, P = 0.005), defined as the maximum distance travelled at depths greater than 200 m. We find no evidence for contemporary transatlantic gene flow (m, M = 0.00) across an oceanic distance of approximately 2400 km. Negaprion acutidens populations in Australia and French Polynesia, separated by oceanic distances of at least 750 km, are moderately differentiated (F(ST) = 0.070-0.087, P < or = 0.001; Phi(ST) = 0.00, P = 0.99), with South Pacific archipelagos probably serving as stepping stones for rare dispersal events. Migration between coastally linked N. brevirostris populations is indicated by nuclear (m = 0.31) but not mitochondrial (m < 0.001) analyses, possibly indicating female natal site fidelity. However, philopatry is equivocal in N. acutidens, which has the lowest control region diversity (h = 0.28) of any shark yet studied. Restricted oceanic dispersal and high coastal connectivity stress the importance of both local and international conservation efforts for these threatened sharks.


Asunto(s)
Genética de Población , Filogenia , Tiburones/genética , Migración Animal , Animales , ADN Mitocondrial/genética , Evolución Molecular , Femenino , Flujo Génico , Especiación Genética , Geografía , Haplotipos , Repeticiones de Microsatélite , Polimorfismo Genético , Análisis de Secuencia de ADN , Tiburones/clasificación , Especificidad de la Especie
17.
Curr Opin Genet Dev ; 4(6): 882-6, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7888759

RESUMEN

The past year has seen a further marshaling of genetic evidence for 'natal homing' in several species of marine turtles, a phenomenon wherein females, upon reaching sexual maturity, exhibit a propensity to return to nest at or near the respective beaches upon which they hatched some two or more decades earlier. This genetics-based inference stems from the strong spatial patterning observed in mitochondrial DNA lineages among nesting sites. Rookery-specific mitochondrial DNA markers are now being employed to monitor the natal sources of individuals captured at other phases of the life cycle, and the genetic findings have important conservation ramifications.


Asunto(s)
ADN Mitocondrial/genética , Comportamiento de Nidificación/fisiología , Tortugas/genética , Animales , Océano Atlántico , Conservación de los Recursos Naturales , Femenino , Marcadores Genéticos , Fenómenos de Retorno al Lugar Habitual , Tortugas/fisiología
18.
AJNR Am J Neuroradiol ; 39(1): 177-183, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29097415

RESUMEN

BACKGROUND AND PURPOSE: Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS: In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS: Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS: Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Traumatismos de los Nervios Periféricos/patología , Nervio Ciático/patología , Animales , Medios de Contraste , Gadolinio DTPA , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Compresión Nerviosa/métodos , Ratas , Ratas Sprague-Dawley , Nervio Ciático/lesiones
19.
J Clin Invest ; 91(6): 2609-19, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7685772

RESUMEN

Blood monocytes are the principal reservoir for tissue macrophages in rheumatoid synovitis. Receptor-mediated adhesive interactions between circulating cells and the synovial venules initiate recruitment. These interactions have been studied primarily in cultured endothelial cells. Thus the functional activities of specific adhesion receptors, such as the endothelial selectins and the leukocytic integrins, have not been evaluated directly in diseased tissues. We therefore examined monocyte-microvascular interactions in rheumatoid synovitis by modifying the Stamper-Woodruff frozen section binding assay initially developed to study lymphocyte homing. Specific binding of monocytes to venules lined by low or high endothelium occurred at concentrations as low as 5 x 10(5) cells/ml. mAbs specific for P-selectin (CD62, GMP-140/PADGEM) blocked adhesion by > 90% in all synovitis specimens examined. In contrast, P-selectin-mediated adhesion to the microvasculature was either lower or absent in frozen sections of normal foreskin and placenta. mAbs specific for E-selectin (ELAM-1) blocked 20-50% of monocyte attachment in several RA synovial specimens but had no effect in others. mAbs specific for LFA-1, Mo1/Mac 1, the integrin beta 2-chain, and L-selectin individually inhibited 30-40% of adhesion. An mAb specific for the integrin beta 1-chain inhibited the attachment of elutriated monocytes up to 20%. We conclude that P-selectin associated with the synovial microvasculature initiates shear-resistant adhesion of monocytes in the Stamper-Woodruff assay and stabilizes bonds formed by other selectins and the integrins. Thus the frozen section binding assay permits direct evaluation of leukocyte-microvascular adhesive interactions in inflamed tissues and suggests a prominent role for P-selectin in monocyte recruitment in vivo.


Asunto(s)
Artritis Reumatoide/patología , Adhesión Celular , Endotelio Vascular/metabolismo , Microcirculación/fisiopatología , Monocitos/metabolismo , Moléculas de Adhesión Celular/metabolismo , Selectina E , Secciones por Congelación , Humanos , Selectina L , Selectina-P , Glicoproteínas de Membrana Plaquetaria/metabolismo , Sinovitis/patología , Distribución Tisular
20.
Plant Cell ; 5(8): 831-841, 1993 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12271087

RESUMEN

In maize endosperm, genes encoding the 22-kD zein class of storage proteins are regulated by the OPAQUE2 locus. The Opaque2 (O2) protein shares homology with the basic domain/leucine zipper class of transcriptional activators. Using microprojectile bombardment, we have shown that O2 is capable of transactivating a 22-kD zein promoter in maize endosperm suspension cultures and in longitudinal sections of intact endosperm. Two mutant forms of the O2 gene were constructed by deleting regions that encode either the basic domain or the first 175 N-terminal residues of the O2 protein. When either of these mutant O2 genes was coexpressed with wild-type O2 in a maize endosperm expression system, O2-mediated transactivation of the 22-kD zein promoter was inhibited specifically and in a dose-dependent manner. Electrophoretic mobility shift assays and immunoprecipitation studies indicated that the mutant O2 proteins form heterodimers with wild-type O2 in vitro. The mutant lacking the basic domain forms heterodimers with wild-type O2, which can no longer bind DNA. In contrast, the product of the N-terminal truncation allele forms homodimers and heterodimers with wild-type O2, both of which can still bind DNA. Because the N-terminal region contains an activation domain, it is likely that these latter complexes are deficient in transactivation. Dominant negative inhibitors of gene expression, such as those constructed here, provide an alternative to antisense RNA approaches for inactivation of gene function in plants.

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