Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

Distribution of variant rs10974944 of the JAK2 gene in Mestizos and Native Americans from Mexico regarding worldwide association studies with myeloproliferative diseases

The genetic variant rs10974944 (C\u3eG) in the JAK2 gene is associated with a higher risk of myeloproliferative neoplasms (MPNs) by increasing the probability of the somatic mutation V617F in the JAK2 protein. For this reason, we evaluated the distribution of rs10974944 in Mexican populations, including published data from association studies in worldwide populations. We analyzed five Mestizo (admixed) (n= 200) and four Native American population samples from Mexico (n= 200), representing the North, Center, West, and South regions of this country. Therefore, we genotyped rs10974944 by qPCR using Taqman probes. Allele and genotype frequencies were estimated in each population sample. The wild-type allele C, the homozygous C/C, and the heterozygous C/G were the most frequent in all Mexican populations. The genotype distribution in all these population samples were in Hardy-Weinberg equilibrium. Interestingly, genetic distances clustered most of the worldwide patient samples, including to Tarahumaras and Mayas, and they showed differences with Mexican and control samples. Although higher genetic susceptibility to MPNs could be predicted in these Native American populations, the homogeneous allele distribution among Mexican and worldwide control populations, compels to analyze further genetic and non-genetic factors. In brief, although worldwide population samples displayed homogeneous distribution for rs10974944, the genetic clustering of worldwide patients supports the claimed association with myeloproliferative neoplasms

The Responses of Medical General Practitioners to Unreasonable Patient Demand for Antibiotics - A Study of Medical Ethics Using Immersive Virtual Reality

BACKGROUND: Dealing with insistent patient demand for antibiotics is an all too common part of a General Practitioner's daily routine. This study explores the extent to which portable Immersive Virtual Reality technology can help us gain an accurate understanding of the factors that influence a doctor's response to the ethical challenge underlying such tenacious requests for antibiotics (given the threat posed by growing anti-bacterial resistance worldwide). It also considers the potential of such technology to train doctors to face such dilemmas. EXPERIMENT: Twelve experienced GPs and nine trainees were confronted with an increasingly angry demand by a woman to prescribe antibiotics to her mother in the face of inconclusive evidence that such antibiotic prescription is necessary. The daughter and mother were virtual characters displayed in immersive virtual reality. The specific purposes of the study were twofold: first, whether experienced GPs would be more resistant to patient demands than the trainees, and second, to investigate whether medical doctors would take the virtual situation seriously. RESULTS: Eight out of the 9 trainees prescribed the antibiotics, whereas 7 out of the 12 GPs did so. On the basis of a Bayesian analysis, these results yield reasonable statistical evidence in favor of the notion that experienced GPs are more likely to withstand the pressure to prescribe antibiotics than trainee doctors, thus answering our first question positively. As for the second question, a post experience questionnaire assessing the participants' level of presence (together with participants' feedback and body language) suggested that overall participants did tend towards the illusion of being in the consultation room depicted in the virtual reality and that the virtual consultation taking place was really happening

Detección inmunohistoquímica del virus de Epstein-Barr en pacientes con linfoma

El virus de Epstein-Barr es un gammaherpes virus que infecta principalmente a linfocitos B permaneciendo en un estado de latencia en el interior del mismo, pudiendo también infectar a linfocitos T y células epiteliales. La persistencia de la infección viral inmortaliza a los linfocitos y favorece el desarrollo de procesos linfoproliferativos malignos como linfomas. Si bien se conoce que la relación entre la infección crónica del virus y el desarrollo de linfoma, varía de acuerdo al tipo histológico, se incrementa en pacientes inmunocomprometidos y de edad avanzada, la evidencia científica indica no sólo la importancia de este virus como agente infeccioso asociado con la etiología de esta neoplasia, sino también como un marcador asociado a respuesta refractaria y peor supervivencia. El objetivo de este estudio observacional descriptivo, fue detectar la presencia del Epstein-Barr virus por técnicas de inmunohistoquímica empleando anticuerpos monoclonales anti antígeno viral proteína latente de membrana en 86 pacientes con linfoma. La positividad para proteína en el total de pacientes con linfoma fue del 44%, correspondiendo el 20% a pacientes con linfoma de Hodgkin y el 24% a pacientes con linfoma no Hodgkin. La detección del virus en estas enfermedades, contribuye al manejo clínico de las mismas ya que el virus no sólo tiene un rol etiológico, sino además es un marcador pronóstico importante, incluso de interés terapéutico

Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin

Longest Common Prefixes with kk-Errors and Applications

Although real-world text datasets, such as DNA sequences, are far from being uniformly random, average-case string searching algorithms perform significantly better than worst-case ones in most applications of interest. In this paper, we study the problem of computing the longest prefix of each suffix of a given string of length $n$ over a constant-sized alphabet that occurs elsewhere in the string with $k$-errors. This problem has already been studied under the Hamming distance model. Our first result is an improvement upon the state-of-the-art average-case time complexity for non-constant $k$ and using only linear space under the Hamming distance model. Notably, we show that our technique can be extended to the edit distance model with the same time and space complexities. Specifically, our algorithms run in $\mathcal{O}(n \log^k n \log \log n)$ time on average using $\mathcal{O}(n)$ space. We show that our technique is applicable to several algorithmic problems in computational biology and elsewhere

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit