A Novel Tissue-Free Method to Estimate Tumor-Derived Cell-Free DNA Quantity Using Tumor Methylation Patterns.

Estimating the abundance of cell-free DNA (cfDNA) fragments shed from a tumor (i.e., circulating tumor DNA (ctDNA)) can approximate tumor burden, which has numerous clinical applications.

Structure of the PAPP-A complex reveals mechanism of substrate recognition.

Insulin-like growth factor (IGF) signaling is highly conserved and tightly regulated by proteases including Pregnancy-Associated Plasma Protein A (PAPP-A). PAPP-A and its paralog PAPP-A2 are metalloproteases that mediate IGF bioavailability through cleavage of IGF binding proteins (IGFBPs). Here, we present single-particle cryo-EM structures of the catalytically inactive mutant PAPP-A (E483A) in complex with a peptide from its substrate IGFBP5 (PAPP-A) and also in its substrate-free form, by leveraging the power of AlphaFold to generate a high quality predicted model as a starting template.

High-throughput screening for improved microbial cell factories, perspective and promise.

High-throughput screening is a critical part of any industrial strain engineering effort, helping ensure the lowest cost product is produced in the shortest amount of time. Small-scale testing that correlates to manufacturing scale allows rapid strain development with confidence that engineering changes are relevant at-scale. In this review, the current state of high-throughput screening, the technological advances for the next generation strain screening pipeline, and options for implementation are reviewed.

The population dynamics of bacteria in physically structured habitats and the adaptive virtue of random motility.

Why is motility so common in bacteria? An obvious answer to this ecological and evolutionary question is that in almost all habitats, bacteria need to go someplace and particularly in the direction of food. Although the machinery required for motility and chemotaxis (acquiring and processing the information needed to direct movement toward nutrients) are functionally coupled in contemporary bacteria, they are coded for by different sets of genes. Moreover, information that resources are more abundant elsewhere in a habitat would be of no value to a bacterium unless it already had the means to get there.

A nuclear complex of rictor and insulin receptor substrate-2 is associated with albuminuria in diabetic mice.

Background: Signaling events associated with diabetic nephropathy are not well understood. Triangulation of events triggered by unrelated bioactive peptides nephrilin and anephril, both of which inhibit albuminuria in diabetic mice, could reveal a common subset of events associated with albuminuria.

Methods: db/db mice received 20 microg/day anephril or nephrilin for 7 weeks.

Discovering functional novelty in metagenomes: examples from light-mediated processes.

The emerging coverage of diverse habitats by metagenomic shotgun data opens new avenues of discovering functional novelty using computational tools. Here, we apply three different concepts for predicting novel functions within light-mediated microbial pathways in five diverse environments. Using phylogenetic approaches, we discovered two novel deep-branching subfamilies of photolyases (involved in light-mediated repair) distributed abundantly in high-UV environments.

Modularity of stress response evolution.

Responses to extracellular stress directly confer survival fitness by means of complex regulatory networks. Despite their complexity, the networks must be evolvable because of changing ecological and environmental pressures. Although the regulatory networks underlying stress responses are characterized extensively, their mechanism of evolution remains poorly understood.

Early adoption of new drug treatments: the role of continuing medical education and physician adaptivity.

The influence of continuing medical education (CME) on the adoption of new treatments is widely regarded as self-evident. Less well understood is how the dynamics of dissemination of new healthcare practices are influenced by the intersection of education with the adaptive characteristics of providers. We developed and validated a 43-item online instrument (eSAIL) for measuring adaptive style and used it to investigate the interplay of physician adaptivity with key components of effective medical education.

Protein function space: viewing the limits or limited by our view?

Given that the number of protein functions on earth is finite, the rapid expansion of biological knowledge and the concomitant exponential increase in the number of protein sequences should, at some point, enable the estimation of the limits of protein function space. The functional coverage of protein sequences can be investigated using computational methods, especially given the massive amount of data being generated by large-scale environmental sequencing (metagenomics). In completely sequenced genomes, the fraction of proteins to which at least some functional features can be assigned has recently risen to as much as approximately 85%.