749 research outputs found
Abundant Human DNA Contamination Identified in Non-Primate Genome Databases
During routine screens of the NCBI databases using human repetitive elements we discovered an unlikely level of nucleotide identity across a broad range of phyla. To ascertain whether databases containing DNA sequences, genome assemblies and trace archive reads were contaminated with human sequences, we performed an in depth search for sequences of human origin in non-human species. Using a primate specific SINE, AluY, we screened 2,749 non-primate public databases from NCBI, Ensembl, JGI, and UCSC and have found 492 to be contaminated with human sequence. These represent species ranging from bacteria (B. cereus) to plants (Z. mays) to fish (D. rerio) with examples found from most phyla. The identification of such extensive contamination of human sequence across databases and sequence types warrants caution among the sequencing community in future sequencing efforts, such as human re-sequencing. We discuss issues this may raise as well as present data that gives insight as to how this may be occurring
High resolution dynamical mapping of social interactions with active RFID
In this paper we present an experimental framework to gather data on
face-to-face social interactions between individuals, with a high spatial and
temporal resolution. We use active Radio Frequency Identification (RFID)
devices that assess contacts with one another by exchanging low-power radio
packets. When individuals wear the beacons as a badge, a persistent radio
contact between the RFID devices can be used as a proxy for a social
interaction between individuals. We present the results of a pilot study
recently performed during a conference, and a subsequent preliminary data
analysis, that provides an assessment of our method and highlights its
versatility and applicability in many areas concerned with human dynamics
Programmable in situ amplification for multiplexed imaging of mRNA expression
In situ hybridization methods enable the mapping of mRNA expression within intact biological samples. With current approaches, it is challenging to simultaneously map multiple target mRNAs within whole-mount vertebrate embryos, representing a significant limitation in attempting to study interacting regulatory elements in systems most relevant to human development and disease. Here, we report a multiplexed fluorescent in situ hybridization method based on orthogonal amplification with hybridization chain reactions (HCR). With this approach, RNA probes complementary to mRNA targets trigger chain reactions in which fluorophore-labeled RNA hairpins self-assemble into tethered fluorescent amplification polymers. The programmability and sequence specificity of these amplification cascades enable multiple HCR amplifiers to operate orthogonally at the same time in the same sample. Robust performance is achieved when imaging five target mRNAs simultaneously in fixed whole-mount and sectioned zebrafish embryos. HCR amplifiers exhibit deep sample penetration, high signal-to-background ratios and sharp signal localization
Quantum phase transition in a single-molecule quantum dot
Quantum criticality is the intriguing possibility offered by the laws of
quantum mechanics when the wave function of a many-particle physical system is
forced to evolve continuously between two distinct, competing ground states.
This phenomenon, often related to a zero-temperature magnetic phase transition,
can be observed in several strongly correlated materials such as heavy fermion
compounds or possibly high-temperature superconductors, and is believed to
govern many of their fascinating, yet still unexplained properties. In contrast
to these bulk materials with very complex electronic structure, artificial
nanoscale devices could offer a new and simpler vista to the comprehension of
quantum phase transitions. This long-sought possibility is demonstrated by our
work in a fullerene molecular junction, where gate voltage induces a crossing
of singlet and triplet spin states at zero magnetic field. Electronic tunneling
from metallic contacts into the quantum dot provides here the
necessary many-body correlations to observe a true quantum critical behavior.Comment: 8 pages, 5 figure
A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes
Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties
The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation
We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol) and sacB (which allows counter-selection using sucrose) flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331), which is the most prevalent in the UK, and 15 (HS143). By screening clinical isolates of other serovars, it should be possible to identify other amenable strains
Simulation of an SEIR infectious disease model on the dynamic contact network of conference attendees
The spread of infectious diseases crucially depends on the pattern of
contacts among individuals. Knowledge of these patterns is thus essential to
inform models and computational efforts. Few empirical studies are however
available that provide estimates of the number and duration of contacts among
social groups. Moreover, their space and time resolution are limited, so that
data is not explicit at the person-to-person level, and the dynamical aspect of
the contacts is disregarded. Here, we want to assess the role of data-driven
dynamic contact patterns among individuals, and in particular of their temporal
aspects, in shaping the spread of a simulated epidemic in the population.
We consider high resolution data of face-to-face interactions between the
attendees of a conference, obtained from the deployment of an infrastructure
based on Radio Frequency Identification (RFID) devices that assess mutual
face-to-face proximity. The spread of epidemics along these interactions is
simulated through an SEIR model, using both the dynamical network of contacts
defined by the collected data, and two aggregated versions of such network, in
order to assess the role of the data temporal aspects.
We show that, on the timescales considered, an aggregated network taking into
account the daily duration of contacts is a good approximation to the full
resolution network, whereas a homogeneous representation which retains only the
topology of the contact network fails in reproducing the size of the epidemic.
These results have important implications in understanding the level of
detail needed to correctly inform computational models for the study and
management of real epidemics
Has carbohydrate-restriction been forgotten as a treatment for diabetes mellitus? A perspective on the ACCORD study design
Prior to the discovery of medical treatment for diabetes, carbohydrate-restriction was the predominant treatment recommendation to treat diabetes mellitus. In this commentary we argue that carbohydrate-restriction should be reincorporated into contemporary treatment studies for diabetes mellitus
Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients
<p>Abstract</p> <p>Background</p> <p>Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic.</p> <p>Methods</p> <p>Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed.</p> <p>Results</p> <p>The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine.</p> <p>Conclusion</p> <p>Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.</p
- …