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1 Eusebio Jiménez López, Centro de Aplicación y Desarrollo de Tecnología de la Universidad Tecnológica del Sur de Sonora, México, Dr. Norman. E. Borlaug Km 14 CP. 85000, (01-644) 414-86-87 Cd. Obregón Sonora, México, ejimenezl@msn.com 2... more
1 Eusebio Jiménez López, Centro de Aplicación y Desarrollo de Tecnología de la Universidad Tecnológica del Sur de Sonora, México, Dr. Norman. E. Borlaug Km 14 CP. 85000, (01-644) 414-86-87 Cd. Obregón Sonora, México, ejimenezl@msn.com 2 Luis Reyes Ávila, Grupo ...
The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that... more
The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human pheno...
There is now clear evidence that asthma prevalence increased significantly, especially in developed countries, during the second part of the 20th century. What caused this increase is currently unknown. Recent reports from the United... more
There is now clear evidence that asthma prevalence increased significantly, especially in developed countries, during the second part of the 20th century. What caused this increase is currently unknown. Recent reports from the United States and the United Kingdom suggest that asthma prevalence may have plateaued between 1995 and the first few years of the present century. This stabilization, and even some decrease in asthma prevalence, especially in countries with high baseline rates, was confirmed by the International Study of Asthma and Allergies in Children. The hospitalization rate for asthma (as a proportion of asthma patients) decreased significantly in the United States between 1980 and 1995, then remained stable between 2001 and 2004. However, the asthma death rate (as a proportion of subjects with asthma) did not decrease significantly during either of those periods. A better understanding of what determines the stable asthma death rate is urgently needed, especially since ...
In the developing countries of the world, an aging of the population in general is occurring at the same time that the life expectancy of older adults is increasing. The results of this double aging process are especially striking for... more
In the developing countries of the world, an aging of the population in general is occurring at the same time that the life expectancy of older adults is increasing. The results of this double aging process are especially striking for health care services because of the concurrent ...
Dubowitz syndrome (DS) is an autosomal recessive disorder characterized by the constellation of mild microcephaly, growth and mental retardation, eczema and peculiar facies. Over 140 cases have been reported, but the genetic basis is not... more
Dubowitz syndrome (DS) is an autosomal recessive disorder characterized by the constellation of mild microcephaly, growth and mental retardation, eczema and peculiar facies. Over 140 cases have been reported, but the genetic basis is not understood. We enrolled a multiplex consanguineous family from the United Arab Emirates with many of the key clinical features of DS as reported in previous series. The family was analyzed by whole exome sequencing. RNA splicing was evaluated with reverse-transcriptase PCR, immunostaining and western blotting was performed with specific antibodies, and site-specific cytosine-5-methylation was studied with bisulfite sequencing. We identified a homozygous splice mutation in the NSUN2 gene, encoding a conserved RNA methyltransferase. The mutation abolished the canonical splice acceptor site of exon 6, leading to use of a cryptic splice donor within an AluY and subsequent mRNA instability. Patient cells lacked NSUN2 protein and there was resultant loss of site-specific 5-cytosine methylation of the tRNA(Asp GTC) at C47 and C48, known NSUN2 targets. Our findings establish NSUN2 as the first causal gene with relationship to the DS spectrum phenotype. NSUN2 has been implicated in Myc-induced cell proliferation and mitotic spindle stability, which might help explain the varied clinical presentation in DS that can include chromosomal instability and immunological defects.
Aortic dissection or rupture resulting from aneurysm causes 1-2% of deaths in developed countries. These disorders are associated with mutations in genes that impact vascular smooth muscle cell (VSMC) differentiation and contractility or... more
Aortic dissection or rupture resulting from aneurysm causes 1-2% of deaths in developed countries. These disorders are associated with mutations in genes that impact vascular smooth muscle cell (VSMC) differentiation and contractility or extracellular matrix (ECM) composition and assembly. However, up to 75% of patients with a family history of aortic aneurysms do not have an identified genetic syndrome. To determine the role of the protease MMP17/MT4-MMP in the arterial wall and its possible relevance in human aortic pathology. Screening of patients with inherited thoracic aortic aneurysm and dissections (TAAD) identified a missense mutation (R373H) in the MMP17 gene that prevented expression of the protease in human transfected cells. Using a loss-of-function genetic mouse model, we demonstrated that the lack of Mmp17 resulted in the presence of dysfunctional VSMCs and altered ECM in the vessel wall; and it led to increased susceptibility to angiotensin II-induced thoracic aortic ...
Page 1. A PHOTOGRAMMETRIC METHOD FOR THE ASSESSMENT OF FACIAL MORPHOLOGY IN FETAL ALCOHOL SYNDROME SCREENING Tania S. Douglas a, *, Fernando Martineza, Ernesta M. Meintjes a, Christopher L. Vaughan a, Denis L. Viljoen b ...
The causal and interplay mechanisms of Single Nucleotide Polymorphisms (SNPs) associated with complex diseases (complex disease SNPs) investigated in genome-wide association studies (GWAS) at the transcriptional level (mRNA) are poorly... more
The causal and interplay mechanisms of Single Nucleotide Polymorphisms (SNPs) associated with complex diseases (complex disease SNPs) investigated in genome-wide association studies (GWAS) at the transcriptional level (mRNA) are poorly understood despite recent advancements such as discoveries reported in the Encyclopedia of DNA Elements (ENCODE) and Genotype-Tissue Expression (GTex). Protein interaction network analyses have successfully improved our understanding of both single gene diseases (Mendelian diseases) and complex diseases. Whether the mRNAs downstream of complex disease genes are central or peripheral in the genetic information flow relating DNA to mRNA remains unclear and may be disease-specific. Using expression Quantitative Trait Loci (eQTL) that provide DNA to mRNA associations and network centrality metrics, we hypothesize that we can unveil the systems properties of information flow between SNPs and the transcriptomes of complex diseases. We compare different cond...
Colorectal cancer (CRC) disproportionately affects American Indians and is a leading cause of mortality despite being treatable when detected early. To better understand the level of provider CRC education and awareness, a survey was... more
Colorectal cancer (CRC) disproportionately affects American Indians and is a leading cause of mortality despite being treatable when detected early. To better understand the level of provider CRC education and awareness, a survey was administered to 33 healthcare providers serving American Indians in California. Demographic data, provider knowledge of screening guidelines, communication, and cultural competency was measured. Data was analyzed using Chi Square and Fischer's Exact Test. In screening guidelines, the majority scored high on FOBT (57.57%); however they scored lower in knowledge of flexible sigmoidoscopy (36.37%), colonoscopy (36.37%), colonography (30.30%) and double contrast barium enema (21.21%). In counseling patients, 87.87% recommended the maintenance of proper diet, 36.63% recommended regular exercise and 54.54% recommended limited intake of processed foods/red meats. In areas of CRC knowledge, more than 80% of providers answered questions correctly. Sixty-four...
Fatigue is one of the most common and perplexing symptoms experienced by cancer survivors. Cancer-related fatigue can be acute or chronic and can persist for years after cancer treatment is completed, negatively impacting a survivor's... more
Fatigue is one of the most common and perplexing symptoms experienced by cancer survivors. Cancer-related fatigue can be acute or chronic and can persist for years after cancer treatment is completed, negatively impacting a survivor's quality of life and ability to function. Often the origin of persistent fatigue is unknown, and there are no validated treatments. This paper reports on the identification, meaning and the lived experience of cancer-related fatigue as reported by American Indian cancer survivors in the Southwest United States. Part of a larger study, key informant interviews (n=20) at an urban Indian hospital and focus groups (n=126) at urban clinics and rural reservation sites collected qualitative data on cancer survivor experiences with fatigue. The sessions were audiotaped and transcribed verbatim. Transcriptions were analyzed, and common themes were coded and formed into categories following Grounded Theory analytical procedures. Relationships between categori...
Colorectal cancer (CRC) disproportionately affects American Indians and is a leading cause of mortality despite being treatable when detected early. An explanatory model to guide a CRC screening education media campaign was developed from... more
Colorectal cancer (CRC) disproportionately affects American Indians and is a leading cause of mortality despite being treatable when detected early. An explanatory model to guide a CRC screening education media campaign was developed from survey and focus group data collected at three American Indian communities (n = 29) in California. Project data was analyzed using Chi Square, Fisher's Exact Test and thematic analysis. Low perceived susceptibility due to low harm value, cultural illness beliefs, and competing priorities likely lead to poor CRC screening behavior, placing American Indians at high risk for CRC mortality.
Genetic studies of asthma have been plagued by a remarkable difficulty in constantly replicating results in different populations for most of the polymorphisms studied. This was true even when the quality of the study design and... more
Genetic studies of asthma have been plagued by a remarkable difficulty in constantly replicating results in different populations for most of the polymorphisms studied. This was true even when the quality of the study design and statistical power were not an issue. The most plausible explanation for these inconsistent results is that genetic polymorphisms, in most cases, do not directly influence risk for asthma but instead modulate the effect of environmental exposures on the inception and clinical expression of asthma and allergies. A better understanding of the genetics of asthma is thus inseparable from a better understanding of the mechanisms by which environmental factors increase the risk for asthma or protect against it.
Chronic exposure to toxicants alters immune function that can affect the ability of the host to mount a response to infection. Giardiasis is a gastrointestinal disease in which subtle alteration in immunity of the host can transform the... more
Chronic exposure to toxicants alters immune function that can affect the ability of the host to mount a response to infection. Giardiasis is a gastrointestinal disease in which subtle alteration in immunity of the host can transform the normal acute infection into a chronic one. In this work we used a murine giardiasis model to evaluate the effect of chronic oral intoxication with sodium arsenite on the characteristics of giardiasis. BALB/c mice were intoxicated during 45 days with water containing 50, 125 or 250 microg/mL sodium arsenite. Each group was then inoculated with G. muris cysts. Cysts excreted in the feces were isolated and quantified. The toxic effect of arsenic on intestinal trophozoites was evaluated using G. lamblia trophozoites cultured in vitro with different arsenic concentrations, corresponding to equivalent concentrations of arsenic found in the gut lumen of intoxicated mice. Mice intoxicated with 125 and 250 microg/mL of sodium arsenite and infected with G. mur...
The L-SCAN (Lau Spreading Center Active-source Investigation) seismic experiment was designed to examine the relationship between melt supply and magmatic, tectonic, and hydrothermal processes along the Eastern Lau Spreading Center (a... more
The L-SCAN (Lau Spreading Center Active-source Investigation) seismic experiment was designed to examine the relationship between melt supply and magmatic, tectonic, and hydrothermal processes along the Eastern Lau Spreading Center (a RIDGE2000 focus site). This 3-D active-source ocean-bottom-seismometer experiment covers a 100-km-long section of the spreading center, which exhibits significant along-strike variability in seafloor morphology, tectonics, and hydrothermal venting. Presumably
ABSTRACT As island arc rifting evolves to mature back-arc spreading, the nature of melt generation and mode of crustal accretion may vary in response to the interplay of different subduction-related processes and conditions, including (1)... more
ABSTRACT As island arc rifting evolves to mature back-arc spreading, the nature of melt generation and mode of crustal accretion may vary in response to the interplay of different subduction-related processes and conditions, including (1) changes in mantle dynamics from flux-melting and buoyancy-driven upwelling at the arc volcanic front to decompression melting driven by plate separation at back-arc spreading centers; (2) re-circulation of refractory material through arc and back-arc melting regimes by mantle wedge corner flow; (3) changes in the locus of magmatic centers relative to the arc volcanic front; (4) variable locus of initial rifting and breakup; (5) spatially varying rheology attributable to mantle wedge hydration gradients with distance from the slab; (6) slab subduction rate, dip, and length. We discuss the possible influence of these factors on crustal accretion processes in light of observations from intra-oceanic back-arc basins, with particular focus on new compilations of swath bathymetry and sidescan imagery from the Lau Basin. In the Lau Basin south of 18°S, the active spreading centers undergo large changes in morphology and crustal characteristics as they separate from the arc volcanic front. Ahead of the southern limit of organized seafloor spreading, a broad area of high acoustic backscatter indicates a wide, "distributed" form of crustal accretion. Parts of the western Lau Basin have been previously interpreted as remnants of a tectonically rifted preexisting arc. The swath mapping data show, however, that western basin morphology is similar to that formed by the sites of currently active magmatic crustal accretion to the east. These observations support a revised model of Lau Basin evolution in which essentially the entire back-arc basin is formed by magmatic crustal accretion, but crustal thickness and morphology reflect the changing locus of the magmatic centers with respect to a mantle wedge of varying chemical fertility and rheology. Compared to mid-ocean settings, the observations imply an expanded range of crustal accretion variables in arc-proximal magmatic centers in which seafloor morphology is more indicative of mantle wedge chemistry than spreading rate.
Significant advances have been made in our understanding of the role of genetic variation in determining complex human phenotypes such as asthma. It is now well established that there is no single ''gene for asthma'', in... more
Significant advances have been made in our understanding of the role of genetic variation in determining complex human phenotypes such as asthma. It is now well established that there is no single ''gene for asthma'', in the way that the cystic fibrosis transmembrane receptor is the ''gene for cystic fibrosis''. It is also clear that among all genetic variants eventually
During June-July 2007 we surveyed the Reykjanes Ridge system south of Iceland to investigate the origin of the V-shaped ridges seen in both bathymetry and gravity, 1st identified by Vogt, and usually interpreted as evidence for pulsing... more
During June-July 2007 we surveyed the Reykjanes Ridge system south of Iceland to investigate the origin of the V-shaped ridges seen in both bathymetry and gravity, 1st identified by Vogt, and usually interpreted as evidence for pulsing Iceland plume material flowing down an axial conduit. However, there are 2 processes that can produce V-shaped wakes along ridges: flow down an existing axis, and rift propagation. Flow down the pipe models, whether of magma pulses (Vogt, 1971) or magma deficits (Hardarson et al., 1997), predict V-wakes symmetric about the axis, whereas the propagating rift model predicts asymmetries caused by the lithospheric transfer. Contrary to previous interpretations from south of 62 N which suggested simple and continuous ridge evolution, and symmetric V wakes consistent with flow down the pipe models, our survey between 62 N and Iceland found evidence for multiple ridge reorganizations caused by new rifts propagating south from Iceland, and asymmetric V wakes....
A set of six synthetic overlapping oligonucleotides coding for noxiustoxin were coupled into a continuous DNA fragment by means of recursive polymerase chain reaction. The polymerase chain reaction product was digested with SalI and... more
A set of six synthetic overlapping oligonucleotides coding for noxiustoxin were coupled into a continuous DNA fragment by means of recursive polymerase chain reaction. The polymerase chain reaction product was digested with SalI and HindIII, ligated into the E, coli vector pCSP 105 and expressed as a fusion protein. The fusion protein was purified and digested with trypsin and the hydrolysis products were separated by high-performance liquid chromatography. Approximately 1.3 mg of recombinant noxiustoxin per liter of culture was obtained. Amino acid analysis and N-terminal amino acid sequence of the recombinant noxiustoxin confirmed the nucleotide sequence of the cloned DNA. Binding experiments using rat brain synaptosomal membranes revealed that recombinant noxiustoxin displaced bound radioactive native NTX with a similar efficiency to cold native noxiustoxin.
Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and... more
Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and ...

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