3,978 research outputs found
Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.
Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism
All-Versus-Nothing Proof of Einstein-Podolsky-Rosen Steering
Einstein-Podolsky-Rosen steering is a form of quantum nonlocality
intermediate between entanglement and Bell nonlocality. Although Schr\"odinger
already mooted the idea in 1935, steering still defies a complete
understanding. In analogy to "all-versus-nothing" proofs of Bell nonlocality,
here we present a proof of steering without inequalities rendering the
detection of correlations leading to a violation of steering inequalities
unnecessary. We show that, given any two-qubit entangled state, the existence
of certain projective measurement by Alice so that Bob's normalized conditional
states can be regarded as two different pure states provides a criterion for
Alice-to-Bob steerability. A steering inequality equivalent to the
all-versus-nothing proof is also obtained. Our result clearly demonstrates that
there exist many quantum states which do not violate any previously known
steering inequality but are indeed steerable. Our method offers advantages over
the existing methods for experimentally testing steerability, and sheds new
light on the asymmetric steering problem.Comment: 7 pages, 2 figures. Accepted in Sci. Re
A systematic review of current knowledge of HIV epidemiology and of sexual behaviour in Nepal
OBJECTIVE: To systematically review information on HIV epidemiology and on sexual behaviour in Nepal with a view to identifying gaps in current knowledge.
METHODS: Systematic review covering electronic databases, web-based information, personal contact with experts and hand searching of key journals.
RESULTS: HIV-1 seroprevalence has been rising rapidly in association with high-risk behaviours, with current levels of 40% amongst the nation's injecting drug users and approaching 20% amongst Kathmandu's female commercial sex workers (FCSWs). HIV seroprevalence remains low in the general population (0.29% of 15â49 year olds). There are significant methodological limitations in many of the seroprevalence studies identified, and these estimates need to be treated with caution. There are extensive migration patterns both within the country and internationally which provide the potential for considerable sexual networking. However, studies of sexual behaviour have focused on FCSWs and the extent of sexual networks within the general population is largely unknown.
CONCLUSIONS: Whilst some of the ingredients are present for an explosive HIV epidemic in Nepal, crucial knowledge on sexual behaviour in the general population is missing. Research on sexual networking is urgently required to guide HIV control in Nepal. There is also a need for further good-quality epidemiological studies of HIV seroprevalence
Mesoscopic structure and social aspects of human mobility
The individual movements of large numbers of people are important in many
contexts, from urban planning to disease spreading. Datasets that capture human
mobility are now available and many interesting features have been discovered,
including the ultra-slow spatial growth of individual mobility. However, the
detailed substructures and spatiotemporal flows of mobility - the sets and
sequences of visited locations - have not been well studied. We show that
individual mobility is dominated by small groups of frequently visited,
dynamically close locations, forming primary "habitats" capturing typical daily
activity, along with subsidiary habitats representing additional travel. These
habitats do not correspond to typical contexts such as home or work. The
temporal evolution of mobility within habitats, which constitutes most motion,
is universal across habitats and exhibits scaling patterns both distinct from
all previous observations and unpredicted by current models. The delay to enter
subsidiary habitats is a primary factor in the spatiotemporal growth of human
travel. Interestingly, habitats correlate with non-mobility dynamics such as
communication activity, implying that habitats may influence processes such as
information spreading and revealing new connections between human mobility and
social networks.Comment: 7 pages, 5 figures (main text); 11 pages, 9 figures, 1 table
(supporting information
Validating child vaccination status in a demographic surveillance system using data from a clinical cohort study: evidence from rural South Africa
<p><b>Background:</b> Childhood vaccination coverage can be estimated from a range of sources. This study aims to validate vaccination data from a longitudinal population-based demographic surveillance system (DSS) against data from a clinical cohort study.</p>
<p><b>Methods:</b> The sample includes 821 children in the Vertical Transmission cohort Study (VTS), who were born between December 2001 and April 2005, and were matched to the Africa Centre DSS, in northern KwaZulu-Natal. Vaccination information in the surveillance was collected retrospectively, using standardized questionnaires during bi-annual household visits, when the child was 12 to 23 months of age. DSS vaccination information was based on extraction from a vaccination card or, if the card was not available, on maternal recall. In the VTS, vaccination data was collected at scheduled maternal and child clinic visits when a study nurse administered child vaccinations. We estimated the sensitivity of the surveillance in detecting vaccinations conducted as part of the VTS during these clinic visits.</p>
<p><b>Results:</b> Vaccination data in matched children in the DSS was based on the vaccination card in about two-thirds of the cases and on maternal recall in about one-third. The sensitivity of the vaccination variables in the surveillance was high for all vaccines based on either information from a South African Road-to-Health (RTH) card (0.94-0.97) or maternal recall (0.94-0.98). Addition of maternal recall to the RTH card information had little effect on the sensitivity of the surveillance variable (0.95-0.97). The estimates of sensitivity did not vary significantly, when we stratified the analyses by maternal antenatal HIV status. Addition of maternal recall of vaccination status of the child to the RTH card information significantly increased the proportion of children known to be vaccinated across all vaccines in the DSS.</p>
<p><b>Conclusion:</b> Maternal recall performs well in identifying vaccinated children aged 12-23 months (both in HIV-infected and HIV-uninfected mothers), with sensitivity similar to information extracted from vaccination cards. Information based on both maternal recall and vaccination cards should be used if the aim is to use surveillance data to identify children who received a vaccination.</p>
A semiconductor source of triggered entangled photon pairs?
The realisation of a triggered entangled photon source will be of great
importance in quantum information, including for quantum key distribution and
quantum computation. We show here that: 1) the source reported in ``A
semiconductor source of triggered entangled photon pairs''[1. Stevenson et al.,
Nature 439, 179 (2006)]} is not entangled; 2) the entanglement indicators used
in Ref. 1 are inappropriate, relying on assumptions invalidated by their own
data; and 3) even after simulating subtraction of the significant quantity of
background noise, their source has insignificant entanglement.Comment: 5 pages in pre-print format, 1 tabl
Structural Causes of Right Bundle Branch BlockâTime for a Closer Look?
Right bundle branch block is an electrocardiographic phenomenon with specific criteria
Influence of the initial chemical conditions on the rational design of silica particles
The influence of the water content in the initial composition on the size of silica particles produced using the StĂśber process is well known. We have shown that there are three morphological regimes defined by compositional boundaries. At low water levels (below stoichiometric ratio of water:tetraethoxysilane), very high surface area and aggregated structures are formed; at high water content (>40 wt%) similar structures are also seen. Between these two boundary conditions, discrete particles are formed whose size are dictated by the water content. Within the compositional regime that enables the classical StĂśber silica, the structural evolution shows a more rapid attainment of final particle size than the rate of formation of silica supporting the monomer addition hypothesis. The clearer understanding of the role of the initial composition on the output of this synthesis method will be of considerable use for the establishment of reliable reproducible silica production for future industrial adoption
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Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa.
Marburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case-fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats
Gene mobility promotes the spread of resistance in bacterial populations
Theory predicts that horizontal gene transfer (HGT) expands the selective conditions under which genes spread in bacterial populations. Whereas vertically inherited genes can only spread by positively selected clonal expansion, mobile genetic elements can drive fixation of genes by infectious HGT. We tested this using populations of Pseudomonas fluorescens and the conjugative mercury resistance (Hg R) plasmid pQBR57. HGT expanded the selective conditions allowing the spread of Hg R: Chromosomal Hg R only increased in frequency under positive selection, whereas plasmid-encoded Hg R reached fixation with or without positive selection. Tracking plasmid dynamics over time revealed that the mode of Hg R inheritance varied across mercury environments. Under mercury selection, the spread of Hg R was driven primarily by clonal expansion while in the absence of mercury Hg R dynamics were dominated by infectious transfer. Thus, HGT is most likely to drive the spread of resistance genes in environments where resistance is useless
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