Cytosolic interactome protects against protein unfolding in a single molecule experiment

Single molecule techniques are particularly well suited for investigating the processes of protein folding and chaperone assistance. However, current assays provide only a limited perspective on the various ways in which the cellular environment can influence the folding pathway of a protein. In this study, a single molecule mechanical interrogation assay is developed and used to monitor protein unfolding and refolding within a cytosolic solution. This allows to test the cumulative topological effect of the cytoplasmic interactome on the folding process. The results reveal a stabilization against forced unfolding for partial folds, which are attributed to the protective effect of the cytoplasmic environment against unfolding and aggregation. This research opens the possibility of conducting single molecule molecular folding experiments in quasi-biological environments.Pharmacolog

Circuit topology approach for the comparative analysis of intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) lack a stable native conformation, making it challenging to characterize their structure and dynamics. Key topological motifs with fundamental biological relevance are often hidden in the conformational noise, eluding detection. Here, we develop a circuit topology toolbox to extract conformational patterns, critical contacts, and timescales from simulated dynamics of intrinsically disordered proteins. We follow the dynamics of IDPs by providing a smart low-dimensionality representation of their three-dimensional (3D) configuration in the topology space. Such an approach allows us to quantify topological similarity in dynamic systems, therefore providing a pipeline for structural comparison of IDPs.Pharmacolog

Pulpal sequelae after trauma to anterior teeth among adult Nigerian dental patients

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies show that about 11.6% to 33.0% of all boys and about 3.6% to 19.3% of all girls suffer dental trauma of varying severity before the age of 12 years. Moderate injuries to the periodontium such as concussion and subluxation are usually associated with relatively minor symptoms and hence may go unnoticed by the patient or the dentist, if consulted. Patients with these kinds of injuries present years after a traumatic accident most of the time with a single discoloured tooth. This study sets out to document the incidence of various posttraumatic sequelae of discoloured anterior teeth among adult Nigerian dental patients.</p> <p>Methods</p> <p>One hundred and sixty eight (168) traumatized discoloured anterior teeth in 165 patients were studied. Teeth with root canal treatment were excluded from the study. Partial obliteration was recorded when the pulp chamber or root canal was not discernible or reduced in size on radiographs, total obliteration was recorded when pulp chamber and root canal were not discernible. A retrospective diagnosis of concussion was made from patient's history of trauma to the tooth without abnormal loosening, while subluxation was made from patient's history of trauma to the tooth with abnormal loosening.</p> <p>Results</p> <p>Of the 168 traumatized discoloured anterior teeth, 47.6% and 31.6% had partial and total obliteration of the pulp canal spaces respectively, 20.8% had pulpal necrosis. Concussion and subluxation injuries resulted more in obliteration of the pulp canal space, while fracture of the teeth resulted in more pulpal necrosis (p < 0.001). Injuries sustained during the 1^stand 2^nddecade of life resulted more in obliteration of the pulp canal space, while injuries sustained in the 3^rddecade resulted in more pulpal necrosis.</p> <p>Conclusion</p> <p>Calcific metamorphosis developed more in teeth with concussion and subluxation injuries. Pulpal necrosis occurred more often in traumatized teeth including fractures.</p

Monitoramento de Phakopsora pachyrhizi na safra 2019/2020 para tomada de decisão do controle químico da ferrugem-asiática da soja.

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Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols

The NANOGrav 15-year Data Set: Evidence for a Gravitational-Wave Background

We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15-year pulsar-timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings-Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law-spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of $10^{14}$, and this same model is favored over an uncorrelated common power-law-spectrum model with Bayes factors of 200-1000, depending on spectral modeling choices. We have built a statistical background distribution for these latter Bayes factors using a method that removes inter-pulsar correlations from our data set, finding $p = 10^{-3}$ (approx. $3\sigma$) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of inter-pulsar correlations yields $p = 5 \times 10^{-5} - 1.9 \times 10^{-4}$ (approx. $3.5 - 4\sigma$). Assuming a fiducial $f^{-2/3}$ characteristic-strain spectrum, as appropriate for an ensemble of binary supermassive black-hole inspirals, the strain amplitude is $2.4^{+0.7}_{-0.6} \times 10^{-15}$ (median + 90% credible interval) at a reference frequency of 1/(1 yr). The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black-hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings-Downs correlations points to the gravitational-wave origin of this signal.Comment: 30 pages, 18 figures. Published in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]