Electric field inversion asymmetry: Rashba and Stark effects for holes in resonant tunneling devices

We report experimental evidence of excitonic spin-splitting, in addition to the conventional Zeeman effect, produced by a combination of the Rashba spin-orbit interaction, Stark shift and charge screening. The electric-field-induced modulation of the spin-splitting are studied during the charging and discharging processes of p-type GaAs/AlAs double barrier resonant tunneling diodes (RTD) under applied bias and magnetic field. The abrupt changes in the photoluminescence, with the applied bias, provide information of the charge accumulation effects on the device.Comment: 4 pages, 2 figure

Variaciones en indicadores geoquímicos (tierras raras e isótopos estables de Carbono) en relación con la paleoprofundidad: ejemplos de depósitos marinos de las Cuencas Neuquina y Austral

Con el objetivo de conocer como varía la composición geoquímica de las aguas con la profundidad y que factores influyen en estos cambios, se realizaron estudios de tierras raras e isótopos estables sobre sucesiones sedimentarias definidas ambientalmente por los métodos tradicionales. A tal fin, se tomaron como casos de estudio secciones sedimentarias de las Formaciones Vaca Muerta, Chachao (Cuenca Neuquina) y Río Mayer (Cuenca Austral), depositadas en forma contemporánea pero a profundidades distintas. Los depósitos de la Cuenca Austral, corresponden a ambientes profundos (plataforma externa) y los indicadores geoquímicos fueron obtenidos a partir de ejemplares de belemnites del género Belemnopsis sp. En la Cuenca Neuquina, los estudios se realizaron en ostras del género Aetostreon sp. acumuladas en ambientes marinos relativamente más someros (rampa externa proximal a rampa media proximal). Estudios petrográficos han permitido confirmar el carácter primario de los valores isotópicos. En la Cuenca Neuquina, las ostras de ambiente marino relativamente más somero muestran un amplio rango de valores de ?13C desde negativos hasta positivos (-4,93 a 2,66‰ VPDB), en tanto que los belemnites de la Cuenca Austral, de ambiente más profundo, poseen menor variabilidad y tenores negativos de ?13C (-1,77 a -0,33‰ VPDB). Asimismo, estos últimos organismos se caracterizan por un enriquecimiento en tierras raras pesadas (valores más elevados de Y/Ho) y de las anomalías de Y, La y Eu, en comparación con los encontrados en las ostras de la Cuenca Neuquina. Se concluye que el contenido de tierras raras e itrio (REY) e isótopos estables en el agua de mar en las cuencas Neuquina y Austral durante el lapso Berriasiano- Valanginiano varió sistemáticamente con la profundidad. En el caso de las REY, este cambio estaría relacionado con la cercanía a las fuentes de aporte de material sedimentario, mientras que la variación en las curvas quimioestratigráficas de carbono se vincularía con la productividad primaria

Valence-band splitting energies in wurtzite InP nanowires : Photoluminescence spectroscopy and ab initio calculations

We investigated experimentally and theoretically the valence-band structure of wurtzite InP nanowires. The wurtzite phase, which usually is not stable for III-V phosphide compounds, has been observed in InP nanowires. We present results on the electronic properties of these nanowires using the photoluminescence excitation technique. Spectra from an ensemble of nanowires show three clear absorption edges separated by 44 meV and 143 meV, respectively. The band edges are attributed to excitonic absorptions involving three distinct valence-bands labeled: A, B, and C. Theoretical results based on"ab initio" calculation gives corresponding valence-band energy separations of 50 meV and 200 meV, respectively, which are in good agreement with the experimental results

Intrinsic Factors Influencing the Infection by Helminth Parasites in Horses under an Oceanic Climate Area (NW Spain)

A coprological survey to determine the influence of some intrinsic factors (breed, age, and sex) on the infection by helminth parasites in equine livestock (n = 418) under an oceanic climate area (NW Spain) was conducted. Faecal samples were individually collected and analyzed by the coprological techniques. The main strongylid genera identified were Trichonema and Cyalocephalus spp (small strongyles) and Strongylus and Triodontophorus (large strongyles). The prevalence of gastrointestinal nematode was 89% (95% CI 86, 92) and 1% cestoda (0, 2). The percentage of horses with strongyloid parasites was 89% (86, 92), 11% (8, 14) for Parascaris, and 3% (1, 5) for Oxyuris. The highest prevalence for ascariosis was observed in the youngest horses (<3 years), for oxyurosis in the >10 years animals, and for strongylosis in the 3–10 years ones. Females were significantly more parasitized than males. A negative correlation between the age and the egg-excretion of ascarids and strongyles was recorded. The autochthonous and the English Pure Blood horses were the most parasitized. We concluded that the infections by helminths, especially the strongyloids, are significantly common in the region, so that greater importance should be given to this situation

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25–30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome. METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants. RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving. CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing

Sprouty2 and Spred1-2 Proteins Inhibit the Activation of the ERK Pathway Elicited by Cyclopentenone Prostanoids

Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA1 and 15d-PGJ2. Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA1-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome.METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants.RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving.CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.</p

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases.

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome. METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants. RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving. CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing