4,232 research outputs found
Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179
The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice
The Power of Non-Determinism in Higher-Order Implicit Complexity
We investigate the power of non-determinism in purely functional programming
languages with higher-order types. Specifically, we consider cons-free programs
of varying data orders, equipped with explicit non-deterministic choice.
Cons-freeness roughly means that data constructors cannot occur in function
bodies and all manipulation of storage space thus has to happen indirectly
using the call stack.
While cons-free programs have previously been used by several authors to
characterise complexity classes, the work on non-deterministic programs has
almost exclusively considered programs of data order 0. Previous work has shown
that adding explicit non-determinism to cons-free programs taking data of order
0 does not increase expressivity; we prove that this - dramatically - is not
the case for higher data orders: adding non-determinism to programs with data
order at least 1 allows for a characterisation of the entire class of
elementary-time decidable sets.
Finally we show how, even with non-deterministic choice, the original
hierarchy of characterisations is restored by imposing different restrictions.Comment: pre-edition version of a paper accepted for publication at ESOP'1
Flavour physics from an approximate U(2)^3 symmetry
The quark sector of the Standard Model exhibits an approximate U(2)^3 flavour
symmetry. This symmetry, broken in specific directions dictated by minimality,
can explain the success of the Cabibbo-Kobayashi-Maskawa picture of flavour
mixing and CP violation, confirmed by the data so far, while allowing for
observable deviations from it, as expected in most models of ElectroWeak
Symmetry Breaking. Building on previous work in the specific context of
supersymmetry, we analyze the expected effects and we quantify the current
bounds in a general Effective Field Theory framework. As a further relevant
example we then show how the U(2)^3 symmetry and its breaking can be
implemented in a generic composite Higgs model and we make a first analysis of
its peculiar consequences. We also discuss how some partial extension of U(2)^3
to the lepton sector can arise, both in general and in composite Higgs models.
An optimistic though conceivable interpretation of the considerations developed
in this paper gives reasons to think that new physics searches in the flavour
sector may be about to explore an interesting realm of phenomena.Comment: 29 pages, 5 figure
Robust gap repair in the contractile ring ensures timely completion of cytokinesis.
Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization-dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure.This project has received funding from the European Research Council
(grants 640553, 260892, and 338410), Fundo Europeu de
Desenvolvimento Regional (FED ER) funds through the Operational
Competitiveness Program (COM PETE), national funds through
Fundação para a Ciência e a Tecnologia (FCT) under the project
FCO MP-01-0124-FED ER-028255 (PTDC/BEX-BCM/0654/2012),
Fundação Luso-Americana para o Desenvolvimento Life Science
2020, and the Louis-Jeantet Young Investigator Award to H. Maiato.
A.X. Carvalho, R. Gassmann, and I.A. Telley have FCT Investigator
positions funded by FCT and cofunded by the European Social Fund
through Programa Operacional Temático Potencial Type 4.2 promotion
of scientific employment. A.M. Silva holds an FCT fellowship
(SFRH/BPD/95707/2013). D.S. Osório was cofunded by the Programa
Operacional Regional do Norte under the Quadro de
Downloaded from jcb.rupress.org on February 27, 2018
Laser microsurgery in the contractile ring • Silva et al. 799
Referência Estratégico Nacional through FED ER and by FCT grant
NOR TE-07-0124-FED ER-000003 (Cell Homeostasis Tissue Organization
and Organism Biology)
ANÁLISE DO CONHECIMENTO DOS ACADÊMICOS DA UNIEVANGÉLICA SOBRE O FLÚOR
O flúor é utilizado na prevenção e controle da doença cárie, pois interfere no processo de desmineralização e remineralização dos dentes. O conhecimento sobre os métodos de utilização do flúor e seus efeitos é importante para toda a população para que o flúor seja utilizado de maneira adequada.
Long-term tobacco exposure and immunosenescence: paradoxical effects on T-cells telomere length and telomerase activity
Immunosenescence are alterations on immune system that occurs throughout an individual life. The main characteristic of this process is replicative senescence, evaluated by telomere shortening. Several factors implicate on telomere shortening, such as smoking. In this study, we evaluated the influence of smoking and Chronic Obstructive Pulmonary Disease (COPD) on cytokines, telomere length and telomerase activity.
Blood samples were collected from subjects aged over 60 years old: Healthy (never smokers), Smokers (smoking for over 30 years) and COPDs (ex-smokers for ≥15 years). A young group was included as control. PBMCs were cultured for assessment of telomerase activity using RT-PCR, and cytokines secretion flow cytometry. CD4+ and CD8+ purified lymphocytes were used to assess telomere length using FlowFISH.
We observed that COPD patients have accelerated telomere shortening. Paradoxically, smokers without lung damage showed preserved telomere length, suggesting that tobacco smoking may affect regulatory mechanisms, such as telomerase. Telomerase activity showed diminished activity in COPDs, while Smokers showed increased activity compared to COPDs and Healthy groups.
Extracellular environment reflected this unbalance, indicated by an anti-inflammatory profile in Smokers, while COPDs showed an inflammatory prone profile. Further studies focusing on telomeric maintenance may unveil mechanisms that are associated with cancer under long-term smoking
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