1,120 research outputs found
Evaluation of warning signs in autism spectrum disorders at the age of 9 to 16 months
Se presenta un estudio ideográfico de seguimiento de un bebé con riesgo de alteración en el
desarrollo. Entre los 9 y los 16 meses de edad se ha registrado en vídeo la conducta espontánea del sujeto
en el entorno del hogar en situaciones de interacción diádica (sujeto-sujeto) y triádica (sujeto-objeto-sujeto).
Para el análisis de datos se establecieron 14 categorías observacionales, basadas en la literatura sobre
desarrollo típico y desarrollo alterado en los Trastornos del Espectro Autista. Los resultados obtenidos
muestran signos de alarma en el desarrollo en todas las edades en las que ha sido estudiado en: seguimiento
de mirada, uso de gestos y conductas de atención (y acción) conjunta. Sería muy aconsejable, introducir
la categoría de Usos de Objetos –usos no convencionales, convencionales, y atípicos– en los instrumentos
para la identificación de los Trastornos del Espectro Autista. Las conclusiones principales señalan la
necesidad de seguir ahondando en el conocimiento de conductas discriminativas desde el primer año de
vida, capaces de alertar sobre un desarrollo alteradoAn ideographic study is presented based on the follow-up of a baby at high risk of impaired
development. The spontaneous behavior of the child was video recorded, in the home environment in situations
of dyadic (subject-subject) and triadic interactions (subject-object-subject). For data analysis, 14
observational categories were established, based on a theoretical review of typical development and
altered development in Autism Spectrum Disorder. Results show warning signs at all ages that were studied,
based on the following aspects: Eye tracking, use of gestures and join attention and action behaviors.
The need to include the category of uses –non-conventional, conventional and atypical uses– of objects in
the instruments and guidelines for the identification of Autism Spectrum Disorders was considered. The
main finding indicates the need to deepen knowledge of discriminative behavior in the first year of life,
useful to identify warning signs of impaired developmentParte de esta investigación ha
sido financiada por el Ministerio de Ciencia e
Innovación. Referencia: EDU2011-2784
9a-Hydroxy-3,8a-dimethyl-5-methylene-4,4a,5,6,9,9a-hexahydronaphtho[2,3-b]furan-2(8aH)-one
The title compound, C15H18O3, was isolated from Lactarius piperatus (Fr.) S. F. Gary collected from the Kunming area in Yunnan province, China. The central cyclohexyl ring adopts a chair conformation, while the furanone ring is close to planar (r.m.s. deviation = 0.0174 Å). The remaining methylene cyclohexene ring has a flattened chair conformation. In the crystal, molecules are linked via intermolecular O—H⋯O and C—H⋯O hydrogen bonds into zigzag chains along the a axis
Ltbp4 regulates Pdgfr beta expression via TGF beta-dependent modulation of Nrf2 transcription factor function
Latent transforming growth factor beta binding protein 4 (LTBP4) belongs to the fibrillin/LTBP family of proteins and plays an important role as a structural component of extracellular matrix (ECM) and local regulator of TGF beta signaling. We have previously reported that Ltbp4S knock out mice (Ltbp4S-/-) develop centrilobular emphysema reminiscent of late stage COPD, which could be partially rescued by inactivating the antioxidant protein Sestrin 2 (Sesn2). More recent studies showed that Sesn2 knock out mice upregulate Pdgfr beta-controlled alveolar maintenance programs that protect against cigarette smoke induced pulmonary emphysema. Based on this, we hypothesized that the emphysema of Ltbp4S-/- mice is primarily caused by defective Pdgfr beta signaling. Here we show that LTBP4 induces Pdgfr beta signaling by inhibiting the antioxidant Nr12/Keap1 pathway in a TGF beta-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair. (C) 2016 The Authors. Published by Elsevier B.V.Peer reviewe
RNA:protein ratio of the unicellular organism as a characteristic of phosphorous and nitrogen stoichiometry and of the cellular requirement of ribosomes for protein synthesis
Background
Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N ratios with the growth rate of organisms indicate a surprising similarity among and within microbial species, plants, and insect herbivores. To reveal the cellular mechanisms underling this similarity, the macromolecular composition of seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed under different conditions of exponential growth.
Results
It was found that P:N ratios calculated from RNA and protein contents in these particular organisms were in the same range as the mean ratios reported for diverse organisms and had similar positive relationships with growth rate, consistent with the growth-rate hypothesis. The efficiency of protein synthesis in microorganisms is estimated as the number of active ribosomes required for the incorporation of one amino acid into the synthesized protein. This parameter is calculated as the SGR:PER ratio. Experimental and theoretical evidence indicated that the requirement of ribosomes for protein synthesis is proportional to the RNA:protein ratio. The constant of proportionality had the same values for all organisms, and was derived mechanistically from the characteristics of the protein-synthesis machinery of the cell (the number of nucleotides per ribosome, the average masses of nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and the fraction of active ribosomes). Impairment of the growth conditions decreased the RNA:protein ratio and increased the overall efficiency of protein synthesis in the microorganisms.
Conclusion
Our results suggest that the decrease in RNA:protein and estimated P:N ratios with decrease in the growth rate of the microorganism is a consequence of an increased overall efficiency of protein synthesis in the cell resulting from activation of the general stress response and increased transcription of cellular maintenance genes at the expense of growth related genes. The strong link between P:N stoichiometry, RNA:protein ratio, ribosomal requirement for protein synthesis, and growth rate of microorganisms indicated by the study could be used to characterize the N and P economy of complex ecosystems such as soils and the oceans
Financial incentives to promote active travel: an evidence review and economic framework
ContextFinancial incentives, including taxes and subsidies, can be used to encourage behavior change. They are common in transport policy for tackling externalities associated with use of motor vehicles, and in public health for influencing alcohol consumption and smoking behaviors. Financial incentives also offer policymakers a compromise between “nudging,” which may be insufficient for changing habitual behavior, and regulations that restrict individual choice.Evidence acquisitionThe literature review identified studies published between January 1997 and January 2012 of financial incentives relating to any mode of travel in which the impact on active travel, physical activity, or obesity levels was reported. It encompassed macroenvironmental schemes, such as gasoline taxes, and microenvironmental schemes, such as employer-subsidized bicycles. Five relevant reviews and 20 primary studies (of which nine were not included in the reviews) were identified.Evidence synthesisThe results show that more-robust evidence is required if policymakers are to maximize the health impact of fiscal policy relating to transport schemes of this kind.ConclusionsDrawing on a literature review and insights from the SLOTH (sleep, leisure, occupation, transportation, and home-based activities) time-budget model, this paper argues that financial incentives may have a larger role in promoting walking and cycling than is acknowledged generally
Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells
Embryonic stem cells (ESC) have the potential to self-renew indefinitely and
to differentiate into any of the three germ layers. The molecular mechanisms
for self-renewal, maintenance of pluripotency and lineage specification are
poorly understood, but recent results point to a key role for epigenetic
mechanisms. In this study, we focus on quantifying the impact of histone 3
acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We
analyze genome-wide histone acetylation patterns and gene expression profiles
measured over the first five days of cell differentiation triggered by
silencing Nanog, a key transcription factor in ESC regulation. We explore the
temporal and spatial dynamics of histone acetylation data and its correlation
with gene expression using supervised and unsupervised statistical models. On a
genome-wide scale, changes in acetylation are significantly correlated to
changes in mRNA expression and, surprisingly, this coherence increases over
time. We quantify the predictive power of histone acetylation for gene
expression changes in a balanced cross-validation procedure. In an in-depth
study we focus on genes central to the regulatory network of Mouse ESC,
including those identified in a recent genome-wide RNAi screen and in the
PluriNet, a computationally derived stem cell signature. We find that compared
to the rest of the genome, ESC-specific genes show significantly more
acetylation signal and a much stronger decrease in acetylation over time, which
is often not reflected in an concordant expression change. These results shed
light on the complexity of the relationship between histone acetylation and
gene expression and are a step forward to dissect the multilayer regulatory
mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog
The compositional and evolutionary logic of metabolism
Metabolism displays striking and robust regularities in the forms of
modularity and hierarchy, whose composition may be compactly described. This
renders metabolic architecture comprehensible as a system, and suggests the
order in which layers of that system emerged. Metabolism also serves as the
foundation in other hierarchies, at least up to cellular integration including
bioenergetics and molecular replication, and trophic ecology. The
recapitulation of patterns first seen in metabolism, in these higher levels,
suggests metabolism as a source of causation or constraint on many forms of
organization in the biosphere.
We identify as modules widely reused subsets of chemicals, reactions, or
functions, each with a conserved internal structure. At the small molecule
substrate level, module boundaries are generally associated with the most
complex reaction mechanisms and the most conserved enzymes. Cofactors form a
structurally and functionally distinctive control layer over the small-molecule
substrate. Complex cofactors are often used at module boundaries of the
substrate level, while simpler ones participate in widely used reactions.
Cofactor functions thus act as "keys" that incorporate classes of organic
reactions within biochemistry.
The same modules that organize the compositional diversity of metabolism are
argued to have governed long-term evolution. Early evolution of core
metabolism, especially carbon-fixation, appears to have required few
innovations among a small number of conserved modules, to produce adaptations
to simple biogeochemical changes of environment. We demonstrate these features
of metabolism at several levels of hierarchy, beginning with the small-molecule
substrate and network architecture, continuing with cofactors and key conserved
reactions, and culminating in the aggregation of multiple diverse physical and
biochemical processes in cells.Comment: 56 pages, 28 figure
Downstream signaling mechanism of the C-terminal activation domain of transcriptional coactivator CoCoA
The coiled-coil coactivator (CoCoA) is a transcriptional coactivator for nuclear receptors and enhances nuclear receptor function by the interaction with the bHLH-PAS domain (AD3) of p160 coactivators. The C-terminal activation domain (AD) of CoCoA possesses strong transactivation activity and is required for the coactivator function of CoCoA with nuclear receptors. To understand how CoCoA AD transmits its activating signal to the transcription machinery, we defined specific subregions, amino acid motifs and protein binding partners involved in the function of CoCoA AD. The minimal transcriptional AD was mapped to approximately 91 C-terminal amino acids and consists of acidic, serine/proline-rich and phenylalanine-rich subdomains. Transcriptional activation by the CoCoA AD was p300-dependent, and p300 interacted physically and functionally with CoCoA AD and was recruited to a promoter by the interaction with CoCoA AD. The FYDVASAF motif in the CoCoA AD was critical for the transcriptional activity of CoCoA AD, the interaction of CoCoA with p300, the coactivator function of CoCoA for estrogen receptor α and GRIP1 and the transcriptional synergy among coactivators GRIP1, CARM1, p300 and CoCoA. Taken together these data extend our understanding of the mechanism of downstream signaling by the essential C-terminal AD of the nuclear receptor coactivator CoCoA; they indicate that p300 is a functionally important interaction partner of CoCoA AD and that their interaction potentiates transcriptional activation by the p160 coactivator complex
Evidence for an oscillatory signature in atmospheric neutrino oscillation
Muon neutrino disappearance probability as a function of neutrino flight
length L over neutrino energy E was studied. A dip in the L/E distribution was
observed in the data, as predicted from the sinusoidal flavor transition
probability of neutrino oscillation. The observed L/E distribution constrained
nu_mu nu_tau neutrino oscillation parameters; 1.9x10^-3 < Delta m^2 <
3.0x10^-3 eV^2 and \sin^2(2theta) > 0.90 at 90% confidence level.Comment: 5 pages, 5 figures, submitted to PR
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