A mouse model with high clonal barcode diversity for joint lineage, transcriptomic, and epigenomic profiling in single cells.

Cellular lineage histories and their molecular states encode fundamental principles of tissue development and homeostasis. Current lineage-recording mouse models have insufficient barcode diversity and single-cell lineage coverage for profiling tissues composed of millions of cells. Here, we developed DARLIN, an inducible Cas9 barcoding mouse line that utilizes terminal deoxynucleotidyl transferase (TdT) and 30 CRISPR target sites.

CoSpar identifies early cell fate biases from single-cell transcriptomic and lineage information.

A goal of single-cell genome-wide profiling is to reconstruct dynamic transitions during cell differentiation, disease onset and drug response. Single-cell assays have recently been integrated with lineage tracing, a set of methods that identify cells of common ancestry to establish bona fide dynamic relationships between cell states. These integrated methods have revealed unappreciated cell dynamics, but their analysis faces recurrent challenges arising from noisy, dispersed lineage data.

Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis.

Bone marrow transplantation therapy relies on the life-long regenerative capacity of haematopoietic stem cells (HSCs). HSCs present a complex variety of regenerative behaviours at the clonal level, but the mechanisms underlying this diversity are still undetermined. Recent advances in single-cell RNA sequencing have revealed transcriptional differences among HSCs, providing a possible explanation for their functional heterogeneity.

Emergence of collective oscillations in adaptive cells.

Collective oscillations of cells in a population appear under diverse biological contexts. Here, we establish a set of common principles by categorising the response of individual cells against a time-varying signal. A positive intracellular signal relay of sufficient gain from participating cells is required to sustain the oscillations, together with phase matching.

Revealing evolutionary constraints on proteins through sequence analysis.

Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein, represented by an additive trait, can give rise to such a sector. As an illustration of a selected trait, we consider the elastic energy of an important conformational change within an elastic network model, and we show that selection acting on this energy leads to correlations among residues.

Inferring energy dissipation from violation of the fluctuation-dissipation theorem.

The Harada-Sasa equality elegantly connects the energy dissipation rate of a moving object with its measurable violation of the Fluctuation-Dissipation Theorem (FDT). Although proven for Langevin processes, its validity remains unclear for discrete Markov systems whose forward and backward transition rates respond asymmetrically to external perturbation. A typical example is a motor protein called kinesin.

Entropy Production of Nanosystems with Time Scale Separation.

Energy flows in biomolecular motors and machines are vital to their function. Yet experimental observations are often limited to a small subset of variables that participate in energy transport and dissipation. Here we show, through a solvable Langevin model, that the seemingly hidden entropy production is measurable through the violation spectrum of the fluctuation-response relation of a slow observable.

Factors Associated with Blood Culture Contamination in the Emergency Department: Critical Illness, End-Stage Renal Disease, and Old Age.

Background: Blood culture contamination in emergency departments (ED) that experience a high volume of patients has negative impacts on optimal patient care. It is therefore important to identify risk factors associated with blood culture contamination in EDs.

Methodology/principal Findings: A prospectively observational study in a university-affiliated hospital were conducted between August 2011 and December 2012.

Rapid Human Immunodeficiency Virus Screening in an Emergency Department in a Region with Low HIV Seroprevalence.

Human immunodeficiency virus (HIV) tests are commonly performed in emergency departments (EDs) in the United States (US), but the experience and effectiveness of conducting rapid HIV tests in EDs in regions with low HIV seroprevalence outside the US have seldom been reported. An observational cross-sectional opt-in rapid HIV test and counseling program was conducted at an ED in a teaching hospital in Taiwan, a country with low seroprevalence, to determine the acceptance of rapid HIV tests as well as risky behaviors and illness presentations of people who agreed to undergo the tests. Among 7,645 ED patients between 20 and 55 years of age, 2,138 (28%) agreed to undergo rapid HIV tests, and only 2 (0.