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1.
Explore (NY) ; 20(5): 102982, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38331693

RESUMEN

Fourteen pairs of twins were selected on the basis of their high scores on The Exceptional Experiences Questionnaire (EEQ), which documents the frequency and intensity of telepathic and synchronistic experiences amongst twins. The twins alternated in the role of sender in which they were exposed to a surprise or shock stimulus and in the role of receiver in which their electrodermal activity (EDA) was monitored. Sender and receiver were placed in laboratory rooms at remote ends of a building separated by distance and barriers ensuring sensory isolation. Twins in the role of sender were presented with a series of surprise or shock stimuli during the period randomly selected for presentation. This was one out of the 8 periods occurring in the block of 5 min. Within the selected period, the actual presentation lasted 30 s and occurred at approximately the midpoint of the period. The stimulus presentation in this block of 5 min was repeated 5 times making thereby a 25-minute session for each twin belonging to the sender-receiver pair. During this session, the other twin in the role of receiver, had been equipped with electrodes recording EDA and otherwise advised to relax during the session. The task for the judge in the studies was to use the electrophysiological data from the non-shocked twin to identify the exact periods when the stimuli had been exposed to the sending twin. The EDA from 91 useable presentations were displayed and analysed for the purpose of locating any peak EDA response in each of the possible eight periods corresponding to the stimuli exposure times. Correct identifications would thus occur by chance one in eight times. The attempts at these identifications were carried out by GB, a researcher experienced at EDA interpretation but blind as to the periods that had been chosen for the stimulus exposure. The findings from the three experimental studies showed there were 18 correct identifications out of the total 91 stimulus exposures (MCE = 11.4), which reached statistical significance on a one-tailed t-test (p = 0.043), and with a binomial test (p = .03, one-tailed). However, only one of the three studies reached significance, in this case at the same level as the collective results (p = 0.043, one-tailed). Two explanations for this are the observed variability in the task-performances of the pairs of twins and in the differences in the sources of the twins for each of the studies. The results of a questionnaire entitled 'Experiences in Close Relationships' (ECR), adapted for twin relationships to assess their degree of attachment, indicated that those twins with many "correct identifications of epochs from the EDA" were not significantly different from the others on this measure of attachment. However, it should be noted that the twins here according to the ECR all had close emotional relationships to each other, thereby giving too little variation to adequately test the hypotheses concerning the role of attachment. The data provides justification for carrying out further studies using this methodology and furthermore that pairs of twins should be used with greater variation in attachment measures. The results are briefly discussed in the context of recent findings concerning the neuropsychology of experiences of synchronicity.

2.
WIREs Water ; 6(2): e1330, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-33362922

RESUMEN

The Fertile Crescent, its hilly flanks and surrounding drylands has been a critical region for studying how climate has influenced societal change, and this review focuses on the region over the last 20,000 years. The complex social, economic, and environmental landscapes in the region today are not new phenomena and understanding their interactions requires a nuanced, multidisciplinary understanding of the past. This review builds on a history of collaboration between the social and natural palaeoscience disciplines. We provide a multidisciplinary, multiscalar perspective on the relevance of past climate, environmental, and archaeological research in assessing present day vulnerabilities and risks for the populations of southwest Asia. We discuss the complexity of palaeoclimatic data interpretation, particularly in relation to hydrology, and provide an overview of key time periods of palaeoclimatic interest. We discuss the critical role that vegetation plays in the human-climate-environment nexus and discuss the implications of the available palaeoclimate and archaeological data, and their interpretation, for palaeonarratives of the region, both climatically and socially. We also provide an overview of how modelling can improve our understanding of past climate impacts and associated change in risk to societies. We conclude by looking to future work, and identify themes of "scale" and "seasonality" as still requiring further focus. We suggest that by appreciating a given locale's place in the regional hydroscape, be it an archaeological site or palaeoenvironmental archive, more robust links to climate can be made where appropriate and interpretations drawn will demand the resolution of factors acting across multiple scales. This article is categorized under:Human Water > Water as Imagined and RepresentedScience of Water > Water and Environmental ChangeWater and Life > Nature of Freshwater Ecosystems.

3.
J Neurointerv Surg ; 6(6): 451-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23943817

RESUMEN

PURPOSE: Newer flat panel angiographic detector (FD) systems have the capability to generate parenchymal blood volume (PBV) maps. The ability to generate these maps in the angiographic suite has the potential to markedly expedite the triage and treatment of patients with acute ischemic stroke. The present study compares FP-PBV maps with cerebral blood volume (CBV) maps derived using standard dynamic CT perfusion (CTP) in a population of patients with stroke. METHODS: 56 patients with cerebrovascular ischemic disease at two participating institutions prospectively underwent both standard dynamic CTP imaging followed by FD-PBV imaging (syngo Neuro PBV IR; Siemens, Erlangen, Germany) under a protocol approved by both institutional review boards. The feasibility of the FD system to generate PBV maps was assessed. The radiation doses for both studies were compared. The sensitivity and specificity of the PBV technique to detect (1) any blood volume deficit and (2) a blood volume deficit greater than one-third of a vascular territory, were defined using standard dynamic CTP CBV maps as the gold standard. RESULTS: Of the 56 patients imaged, PBV maps were technically adequate in 42 (75%). The 14 inadequate studies were not interpretable secondary to patient motion/positioning (n=4), an injection issue (n=2), or another reason (n=8). The average dose for FD-PBV was 219 mGy (median 208) versus 204 mGy (median 201) for CT-CBV. On CT-CBV maps 26 of 42 had a CBV deficit (61.9%) and 15 (35.7%) had a deficit that accounted for greater than one-third of a vascular territory. FD-PBV maps were 100% sensitive and 81.3% specific to detect any CBV deficit and 100% sensitive and 62.9% specific to detect any CBV deficit of greater than one-third of a territory. CONCLUSIONS: PBV maps can be generated using FP systems. The average radiation dose is similar to a standard CTP examination. PBV maps have a high sensitivity for detecting CBV deficits defined by conventional CTP. PBV maps often overestimate the size of CBV deficits. We hypothesize that the FP protocol initiates PBV imaging prior to complete saturation of the blood volume in areas perfused via indirect pathways (ie, leptomeningeal collaterals), resulting in an overestimation of CBV deficits, particularly in the setting of large vessel occlusion.


Asunto(s)
Volumen Sanguíneo , Angiografía Cerebral/instrumentación , Angiografía Cerebral/métodos , Circulación Cerebrovascular , Accidente Cerebrovascular/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Mapeo Encefálico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Dosis de Radiación
4.
PLoS One ; 8(7): e68061, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23894294

RESUMEN

Pre-Pottery Neolithic assemblages are best known from the fertile areas of the Mediterranean Levant. The archaeological site of Jebel Qattar 101 (JQ-101), at Jubbah in the southern part of the Nefud Desert of northern Saudi Arabia, contains a large collection of stone tools, adjacent to an Early Holocene palaeolake. The stone tool assemblage contains lithic types, including El-Khiam and Helwan projectile points, which are similar to those recorded in Pre-Pottery Neolithic A and Pre-Pottery Neolithic B assemblages in the Fertile Crescent. Jebel Qattar lies ∼500 kilometres outside the previously identified geographic range of Pre-Pottery Neolithic cultures. Technological analysis of the typologically diagnostic Jebel Qattar 101 projectile points indicates a unique strategy to manufacture the final forms, thereby raising the possibility of either direct migration of Levantine groups or the acculturation of mobile communities in Arabia. The discovery of the Early Holocene site of Jebel Qattar suggests that our view of the geographic distribution and character of Pre-Pottery Neolithic cultures may be in need of revision.


Asunto(s)
Arqueología , Civilización , Ambiente , Humanos , Arabia Saudita
5.
Explore (NY) ; 9(1): 26-31, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23294817

RESUMEN

Four pairs of monozygotic twins were tested for synchronous responses that occurred in the physiological data of one twin during the period when the other twin was exposed to shock and surprise stimuli. Each of the five stimuli was presented in random order, producing five blocks of trial periods within each 25-minute session per twin. There were eight possible trial periods within each block. The choice of the trial periods, that is, the exact time placement of the shock stimuli within the blocks, was determined randomly. Data from six sessions with the four pairs of twins were used by the same polygraph expert who was successful in a previous study in identifying these trial periods. In accordance with the previously determined protocol for the experiment, six of these trials were passed on, leaving 24 trial blocks for which assessments were made as to which period the stimulus had occurred. Six of these gave hits, whereas three hits were expected by chance and four of these six correct placements were made by one of the pairs of twins. The data provide further justification for a major study in this area using the outlined methodology with selected pairs of twins.


Asunto(s)
Reflejo de Sobresalto , Gemelos Monocigóticos , Adulto , Anciano , Femenino , Humanos , Londres , Persona de Mediana Edad , Monitoreo Fisiológico
6.
PLoS One ; 7(11): e49840, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23185454

RESUMEN

The Arabian Peninsula is a key region for understanding hominin dispersals and the effect of climate change on prehistoric demography, although little information on these topics is presently available owing to the poor preservation of archaeological sites in this desert environment. Here, we describe the discovery of three stratified and buried archaeological sites in the Nefud Desert, which includes the oldest dated occupation for the region. The stone tool assemblages are identified as a Middle Palaeolithic industry that includes Levallois manufacturing methods and the production of tools on flakes. Hominin occupations correspond with humid periods, particularly Marine Isotope Stages 7 and 5 of the Late Pleistocene. The Middle Palaeolithic occupations were situated along the Jubbah palaeolake-shores, in a grassland setting with some trees. Populations procured different raw materials across the lake region to manufacture stone tools, using the implements to process plants and animals. To reach the Jubbah palaeolake, Middle Palaeolithic populations travelled into the ameliorated Nefud Desert interior, possibly gaining access from multiple directions, either using routes from the north and west (the Levant and the Sinai), the north (the Mesopotamian plains and the Euphrates basin), or the east (the Persian Gulf). The Jubbah stone tool assemblages have their own suite of technological characters, but have types reminiscent of both African Middle Stone Age and Levantine Middle Palaeolithic industries. Comparative inter-regional analysis of core technology indicates morphological similarities with the Levantine Tabun C assemblage, associated with human fossils controversially identified as either Neanderthals or Homo sapiens.


Asunto(s)
Arqueología , Evolución Biológica , Hominidae , Hombre de Neandertal , Animales , Arabia , Cambio Climático , Ambiente , Fósiles , Humanos , Paleontología
7.
Explore (NY) ; 8(6): 339-47, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23141790

RESUMEN

OBJECTIVE: Studies of synchronous physiological responses to startle stimuli between monozygotic twins and other paired subjects have suffered from methodological flaws such as post-hoc specifications of "connectedness" criteria. The mechanisms that affect any such connectedness are unknown. With the logistic and financial support of a television company, we conducted a methodological pilot study with predefined objective hit criteria in which we used four pairs of twins with frequent experiences of connectedness. METHODS: While one twin was exposed during a 12-minute period to five randomly presented mild shock or surprise stimuli, the electrodermal activity, blood pressure, breathing, and bodily movements were simultaneously recorded in the second twin. An authorized polygraph expert who was blind to the stimulus exposure times examined the data for deviations from normal physiological patterns during relaxation and delivered precisely timed estimates of such deviations. "Hits" (indications of connectedness) were objectively defined as an estimate lying within a 15-second "hit window." RESULTS: Overall results were nonsignificant, P > .7. However, for one pair of twins, the polygraph expert identified 10 deviating patterns, of which three were hits were P < .03. This data set was sent to a second, independent expert, who blindly identified the same three hits, pointing to only eight patterns, P < .0003. DISCUSSION: We argue that the applied methodology for "hit" identification is objective and recommendable. Speculatively, because the "successful" pair of twins was reported to be monochorionic-monoamnionic (as embryos, they shared the same placenta and the same bag of water), embryonic history might be further investigated as a potential factor for connectedness between monozygotic twins.


Asunto(s)
Presión Sanguínea , Respuesta Galvánica de la Piel , Movimiento , Placenta , Reflejo de Sobresalto , Respiración , Gemelos Monocigóticos , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Proyectos Piloto , Embarazo , Adulto Joven
8.
Clin Cardiol ; 35(10): 641-5, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22949086

RESUMEN

BACKGROUND: Coronary artery atherosclerosis has been associated with obstructive sleep apnea (OSA). However, the type and severity of plaque formation have not been characterized. This study evaluated the association of coronary noncalcified plaques and severity of stenosis in patients with OSA. METHODS: This study was a retrospective analysis of 81 patients, 49 with OSA and 32 without OSA, who had undergone multidetector-row helical computed tomography scanning. The board-certified radiologist was blinded to the diagnosis of OSA and reviewed the scans for plaque characterization, severity of stenosis, and number of vessels involved. RESULTS: Of the 81 patients reviewed, the mean apnea-hypopnea index in the OSA group was 42.2 vs 7.5 in the non-OSA group. The groups did not significantly differ in the distribution of comorbid conditions. We found that among the patients with OSA, 63% had noncalcified/mixed plaques, as opposed to 16% in the non-OSA group (P < 0.0001), with unadjusted odds ratio of 9.3 (3.0, 28.4). After adjustment for other risk factors such as age, sex, race, hypercholesterolemia, and history of smoking, the association remained strong, with an odds ratio of 7.0 (1.9, 26.5; P < 0.05). CONCLUSIONS: Our study finds that the frequency of noncalcified/mixed plaques is much higher in patients with OSA than in non-OSA patients. Patients with OSA also have more severe stenosis and a higher number of vessels involved. This study adds to a growing body of data regarding our understanding of the association of OSA and atherosclerosis.


Asunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria/patología , Apnea Obstructiva del Sueño/patología , Tomografía Computarizada por Rayos X , Intervalos de Confianza , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polisomnografía , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/epidemiología , Estados Unidos/epidemiología
9.
J Interferon Cytokine Res ; 31(7): 527-31, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21574823

RESUMEN

Our primary objective in this study was to determine the differences in inflammatory profile between patients with high risk for obstructive sleep apnea (OSA) versus low risk in a patient population undergoing cardiac rehabilitation and to evaluate the effect of 4 weeks of rehabilitation on cytokine levels in the 2 groups. A total of 20 consecutive patients were screened using the Berlin questionnaire to determine high and low risk of OSA. Of the 20 total consecutive patients, 3 patients did not consent to participate and 1 did not get cytokine analysis. Of the remaining 16 patients (8 men and 8 women), 8 (50%) patients were found to have high risk for OSA as predicted by the Berlin questionnaire. Men predominated the high-risk group (75%). There was a trend of increased cytokine load in the high-risk group; however, it did not reach statistical significance except for monocyte chemoattractant protein-1 (P value=0.02). A significant reduction was noted in cytokine levels after 4 weeks of rehabilitation in the group with OSA, which was statistically significant (P value<0.5). The high-risk group patients had elevated cytokine levels, especially monocyte chemoattractant protein-1. Further, a significant reduction in cytokine levels was noted in the high-risk group after 4 weeks of rehabilitation.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/rehabilitación , Respiración con Presión Positiva , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/rehabilitación , Anciano , Anciano de 80 o más Años , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Enfermedad de la Arteria Coronaria/inmunología , Femenino , Humanos , Terapia de Inmunosupresión , Mediadores de Inflamación/metabolismo , Masculino , Riesgo , Apnea Obstructiva del Sueño/inmunología , Encuestas y Cuestionarios , Resultado del Tratamiento , Regulación hacia Arriba/inmunología
10.
Science ; 331(6016): 453-6, 2011 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-21273486

RESUMEN

The timing of the dispersal of anatomically modern humans (AMH) out of Africa is a fundamental question in human evolutionary studies. Existing data suggest a rapid coastal exodus via the Indian Ocean rim around 60,000 years ago. We present evidence from Jebel Faya, United Arab Emirates, demonstrating human presence in eastern Arabia during the last interglacial. The tool kit found at Jebel Faya has affinities to the late Middle Stone Age in northeast Africa, indicating that technological innovation was not necessary to facilitate migration into Arabia. Instead, we propose that low eustatic sea level and increased rainfall during the transition between marine isotope stages 6 and 5 allowed humans to populate Arabia. This evidence implies that AMH may have been present in South Asia before the Toba eruption.


Asunto(s)
Arqueología , Cambio Climático , Emigración e Inmigración/historia , África , Arabia , Evolución Biológica , Historia Antigua , Humanos , Tiempo , Emiratos Árabes Unidos
11.
J Cardiopulm Rehabil Prev ; 31(3): 188-92, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21240006

RESUMEN

OBJECTIVES: : The primary objective of this study was to determine the prevalence of undiagnosed or untreated obstructive sleep apnea (OSA) in patients undergoing cardiac rehabilitation. METHODS: : A total of 132 consecutive patients were screened by Berlin Questionnaire to determine the presence or absence of OSA. RESULTS: : Fourteen patients did not consent to participate. Of the remaining 118 patients, 20 (17%) were found to have a preexisting formal diagnosis of OSA. Of the remaining 98 patients (69 males and 29 females), 43 (44%) were found to have a high probability of OSA as predicted by the Berlin Questionnaire. There was no significant difference in the prevalence (P < .05) between males (29/69, 42%) and females (14/29, 48%) who were predicted to have OSA. Similarly, no significant differences were observed in the ages or body mass index between OSA and non-OSA patients. A significantly greater frequency (P < .05) of coronary artery disease was observed in the OSA group than in the non-OSA group. CONCLUSIONS: : Overall, the rate of preexisting and predicted OSA (53%) suggests a high prevalence of OSA in patients with cardiovascular diseases in a cardiac rehabilitation setting. Moreover, the high rate of undiagnosed OSA, as suggested by the Berlin Questionnaire, further adds to the growing literature that a large number of patients with significant cardiovascular disease carry the burden of sleep disordered breathing.


Asunto(s)
Rehabilitación Cardiaca , Fármacos Cardiovasculares/uso terapéutico , Polisomnografía , Apnea Obstructiva del Sueño , Anciano , Índice de Masa Corporal , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Errores Diagnósticos/prevención & control , Femenino , Humanos , Masculino , North Carolina/epidemiología , Prevalencia , Factores de Riesgo , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Encuestas y Cuestionarios
13.
Rapid Commun Mass Spectrom ; 23(16): 2398-402, 2009 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-19603477

RESUMEN

Rice (Oryza sativa L.) accumulates large amounts of silicon which improves its growth and health due to enhanced resistance to biotic and abiotic stresses. Silicon uptake and loading to xylem in rice are predominantly active processes performed by transporters encoded by the recently identified genes Lsi1 (Si influx transporter gene) and Lsi2 (Si efflux transporter gene). Silicon deposition in rice during translocation to upper plant tissues is known to discriminate against the heavier isotopes (29)Si and (30)Si, resulting in isotope fractionation within the plant. We analyzed straw and husk samples of rice mutants defective in Lsi1, Lsi2 or both for silicon content and delta(29)Si using isotope ratio mass spectrometry (IRMS) and compared these results with those for the corresponding wild-type varieties (WT). The silicon content was higher in husk than in straw. All the mutant rice lines showed clearly lower silicon content than the WT lines (4-23% Si of WT). The delta(29)Si was lower in straw and husk for the uptake defective mutant (lsi1) than for WT, albeit delta(29)Si was 0.3 per thousand higher in husk than in straw in both lines. The effect of defective efflux (lsi2) differed for straw and husk with higher delta(29)Si in straw, but lower delta(29)Si in husk while WT showed similar delta(29)Si in both fractions. These initial results show the potential of Si isotopes to enlighten the influence of active uptake on translocation and deposition processes in the plant.


Asunto(s)
Isótopos/metabolismo , Oryza/metabolismo , Silicio/metabolismo , Transporte Biológico , Isótopos/química , Espectrometría de Masas , Oryza/química , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estructuras de las Plantas/química , Estructuras de las Plantas/genética , Estructuras de las Plantas/metabolismo , Silicio/química
15.
Mol Cancer Ther ; 5(11): 2606-12, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17088437

RESUMEN

The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.


Asunto(s)
Línea Celular Tumoral , Genes Relacionados con las Neoplasias , Mutación , Análisis Mutacional de ADN , Exones , Eliminación de Gen , Perfilación de la Expresión Génica , Homocigoto , Humanos , Sitios de Empalme de ARN
16.
Nat Genet ; 38(11): 1242-4, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17013395

RESUMEN

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.


Asunto(s)
Proteínas del Citoesqueleto/genética , Genes Ligados a X , Proteínas de la Membrana/genética , Nistagmo Congénito/genética , Encéfalo/embriología , Encéfalo/metabolismo , Mapeo Cromosómico , Cromosomas Humanos X , Proteínas del Citoesqueleto/fisiología , Movimientos Oculares/genética , Movimientos Oculares/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica , Ligamiento Genético , Humanos , Masculino , Proteínas de la Membrana/fisiología , Mutación/fisiología , Linaje , Retina/metabolismo
17.
Cancer Biol Ther ; 5(8): 928-32, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16969076

RESUMEN

An activating point mutation in codon 12 of the HRAS gene was the first somatic point mutation identified in a human cancer and established the role of somatic mutations as the common driver of oncogenesis. Since then, there have been over 11,000 mutations in the three RAS (HRAS, KRAS and NRAS) genes in codons 12, 13 and 61 reported in the literature. We report here the identification of recurrent somatic missense mutations at alanine 146, a highly conserved residue in the guanine nucleotide binding domain. In two independent series of colorectal cancers from Hong Kong and the United States we detected KRAS A146 mutations in 7/126 and 2/94 cases, respectively, giving a combined frequency of 4%. We also detected KRAS A146 mutations in 2/40 (5%) colorectal cell lines, including the NCI-60 colorectal cancer line HCC2998. Codon 146 mutations thus are likely to make an equal or greater contribution to colorectal cancer than codon 61 mutations (4.2% in our combined series, 1% in the literature). Lung adenocarcinomas and large cell carcinomas did not show codon 146 mutations. We did, however, identify a KRAS A146 mutation in the ML-2 acute myeloid leukemia cell line and an NRAS A146 mutation in the NALM-6 B-cell acute lymphoblastic leukemia line, suggesting that the contribution of codon 146 mutations is not entirely restricted to colorectal cancers or to KRAS.


Asunto(s)
Codón/genética , Neoplasias Colorrectales/genética , Genes ras/genética , Mutación Puntual/genética , Adenocarcinoma/genética , Secuencia de Aminoácidos , Carcinoma de Células Grandes/genética , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Hong Kong , Humanos , Leucemia Mieloide Aguda/genética , Datos de Secuencia Molecular , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Homología de Secuencia de Aminoácido , Estados Unidos
18.
Forensic Sci Int ; 162(1-3): 152-62, 2006 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-16875791

RESUMEN

The increase in both automation and precision in the analysis of geological materials has had significant impact upon forensic investigations in the last 10 years. There is however, a fundamental philosophical difference between forensic and geological enquiry. This paper presents the results of forensic geoscientific investigations of three cases of wildlife crime. Two cases involve the analysis of soils recovered after incidents of illegal badger baiting in the United Kingdom. The third case involves the illegal importation of Eleonora's Falcon (Falco eleonorae) into the United Kingdom from the Mediterranean. All three cases utilise the analysis of soils by a variety of physical, chemical and biological techniques. These involve mineral and grain size analyses, cation and anion compositions, pH, organic content and pollen analysis. The independent analysis undertaken by specialists in each of these three main fields conclude firstly, that there is a significant similarity between sediments taken at the crime site at both badger setts and with sediments recovered from various spades, shovels and clothing belonging to suspects and secondly, that the soils analysed associated with the removal of the falcon eggs in the Mediterranean contained characteristics similar in many respects to the soils of the breeding areas of F. eleonorae on the cliffs of Mallorca. The use of these independent techniques in wildlife crime detection has great potential given the ubiquitous nature of soils and sediments found in association with wildlife sites.


Asunto(s)
Conservación de los Recursos Naturales , Crimen , Suelo/análisis , Animales , Falconiformes , Medicina Legal/métodos , Humanos , Concentración de Iones de Hidrógeno , Masculino , Microscopía Electrónica de Rastreo , Minerales/análisis , Mustelidae
19.
Forensic Sci Int ; 162(1-3): 6-12, 2006 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-16919902

RESUMEN

The routine production of a cast of a shoe-print taken in soil provides information other than shoe size and gait. Material adhering to the surface of the cast represents the preservation of the moment of footprint impression. The analysis of the interface between the cast and soil is therefore a potentially lucrative source of information for forensic reconstruction. These principles are demonstrated with reference to a murder case which took place in the English Midlands. The cast of a footprint provided evidence of a two-way transfer of material between the sole of a boot and the soil of a recently ploughed field. Lumps of soil, which had dried on a boot, were deposited on the field as the footprints were made. Pollen analysis of these lumps of soil indicated that the perpetrator of the imprint had been standing recently in a nearby stream. Fibre analysis together with physical and chemical characteristics of the soil suggested a provenance for contamination of this mud prior to deposition of the footprint. Carbon/nitrogen ratios of the water taken from the cast showed that distilled water had been used thus excluding the possibility of contamination of the boot-soil interface. It was possible to reconstruct three phases of previous activity of the wearer of the boot prior to leaving the footprint in the field after the murder had taken place. This analysis shows the power of integrating different independent techniques in the analysis of hitherto unrecognised forensic materials.


Asunto(s)
Medicina Legal/métodos , Zapatos , Suelo/análisis , Carbono/análisis , Femenino , Humanos , Masculino , Microscopía , Minerales/análisis , Nitrógeno/análisis
20.
Cancer Res ; 66(8): 3987-91, 2006 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-16618716

RESUMEN

Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolomide after surgical resection and radiotherapy. Although a statistically significant increase in survival has been reported with this regimen, nearly all gliomas recur and become insensitive to further treatment with this class of agents. We sequenced 500 kb of genomic DNA corresponding to the kinase domains of 518 protein kinases in each of nine gliomas. Large numbers of somatic mutations were observed in two gliomas recurrent after alkylating agent treatment. The pattern of mutations in these cases showed strong similarity to that induced by alkylating agents in experimental systems. Further investigation revealed inactivating somatic mutations of the mismatch repair gene MSH6 in each case. We propose that inactivating somatic mutations of MSH6 confer resistance to alkylating agents in gliomas in vivo and concurrently unleash accelerated mutagenesis in resistant clones as a consequence of continued exposure to alkylating agents in the presence of defective mismatch repair. The evidence therefore suggests that when MSH6 is inactivated in gliomas, alkylating agents convert from induction of tumor cell death to promotion of neoplastic progression. These observations highlight the potential of large scale sequencing for revealing and elucidating mutagenic processes operative in individual human cancers.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/genética , Proteínas de Unión al ADN/genética , Dacarbazina/análogos & derivados , Glioma/genética , Mutación , Recurrencia Local de Neoplasia/genética , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/enzimología , Dacarbazina/uso terapéutico , Femenino , Glioma/tratamiento farmacológico , Glioma/enzimología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/enzimología , Proteínas Quinasas/genética , Temozolomida
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