The chromolinker hypothesis: Are eukaryotic genomes also circular?

Over more than the past century, reports that chromosomes in Eukaryotes are linked have been published. Recently this has been confirmed by micromanipulation. The chromolinkers are DNAse sensitive, as has been previously reported. The arguments for and against chromolinkers have been reviewed, and a call for definitive research made, because if chromolinkers do exist, the whole basis for nuclear DNA genetics may require revision.

The Molecular Basis of Differentiation Wave Activity in Embryogenesis.

As development varies greatly across the tree of life, it may seem difficult to suggest a model that proposes a single mechanism for understanding collective cell behaviors and the coordination of tissue formation. Here we propose a mechanism called differentiation waves, which unify many disparate results involving developmental systems from across the tree of life. We demonstrate how a relatively simple model of differentiation proceeds not from function-related molecular mechanisms, but from so-called differentiation waves. A phenotypic model of differentiation waves is introduced, and its relation to molecular mechanisms is proposed. These waves contribute to a differentiation tree, which is an alternate way of viewing cell lineage and local action of the molecular factors. We construct a model of differentiation wave-related molecular mechanisms (genome, epigenome, and proteome) based on bioinformatic data from the nematode Caenorhabditis elegans. To validate this approach across different modes of development, we evaluate protein expression across different types of development by comparing Caenorhabditis elegans with several model organisms: fruit flies (Drosophila melanogaster), yeast (Saccharomyces cerevisiae), and mouse (Mus musculus). Inspired by gene regulatory networks, two Models of Interactive Contributions (fully-connected MICs and ordered MICs) are used to suggest potential genomic contributions to differentiation wave-related proteins. This, in turn, provides a framework for understanding differentiation and development.

Multifunctional metallic nanocomposite for overcoming the strength-ductility trade-off.

The actualization of high strength and ductility in alloys, in addition to providing strong, formable materials, can lead to reduced weights in practical applications. However, increasing strength typically comes at the cost of lowering the ductility and vice-versa, referred to as the strength-ductility trade-off. In this work, we investigate the thermo-mechanical response of a 3-element multifunctional NiTi-Nb nanocomposite material that overcomes this trade-off, as it exhibits a high strength of 980 MPa and an ultrahigh ductility of 58% at fracture. The remarkable properties are attributed to the underlying microstructure of Nb nanofibers dispersed in an NiTi matrix. Deformation is accommodated via the shape memory transformation of the active NiTi matrix in concert with elastoplastic deformation of Nb nanofibers embedded within the matrix. Consequently, the material exhibits multifunctionality and recovers deformation during heating via the reversion of the stress-induced martensitic transformation in the NiTi matrix. The high strength and high ductility of this 3-element nanocomposite material puts it amongst the best performing high-entropy alloys (HEAs) that are typically made up of five or more elements.

A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Primary aldosteronism: actual epidemics or false alarm?

A prevalência de "hiperaldosteronismo primário" (HAP) não pode ser determinada atualmente com precisão, uma vez que 1) não há uma definição aceita universalmente, e 2) existem fases tanto de normotensão como de normocalemia durante o desenvolvimento evolutivo desta doença eventualmente caracterizada por hipertensão e hipocalemia. A exceção são as formas totalmente caracterizadas geneticamente, como o hiperaldosteronismo supressível por glicocorticóides, cuja real prevalência pode ser comprovada hoje em dia por rastreamento universal, usando uma única amostra de sangue, embora isto não seja nem prático nem apropriado. Controvérsias têm sido levantadas com relação à raridade, ou o contrário, do HAP, devido à 1) redescoberta, nos últimos 12 anos, da fase normocalêmica descrita por Conn, 2) aplicação de métodos amplamente disponíveis para mensuração da aldosterona e renina para "rastreamento", 3) a variável qualidade destes métodos, e sua aplicação, e 4) ausência dos necessários testes "diagnósticos", em adição ao screening, em alguns estudos. HAP é significativamente mais comum do que previamente imaginado, e uma forma muito importante de hipertensão potencialmente curável. O diagnóstico precoce e o tratamento específico evitam a morbidade. O foco atual no aumento da detecção do HAP é essencial, e irá auxiliar a resolver a questão de sua prevalência.