Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer.

Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals.

Sustainable Peptide Synthesis Enabled by a Transient Protecting Group.

The growing interest in synthetic peptides has prompted the development of viable methods for their sustainable production. Currently, large amounts of toxic solvents are required for peptide assembly from protected building blocks, and switching to water as a reaction medium remains a major hurdle in peptide chemistry. We report an aqueous solid-phase peptide synthesis strategy that is based on a water-compatible 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc) protecting group.

Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure.

On March 1 and 2, 2018, the National Institutes of Health 2018 Progenitor Cell Translational Consortium, Cardiovascular Bioengineering Symposium, was held at the University of Alabama at Birmingham. Convergence of life sciences and engineering to advance the understanding and treatment of heart failure was the theme of the meeting. Over 150 attendees were present, and >40 scientists presented their latest work on engineering human functional myocardium for disease modeling, drug development, and heart failure research.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

Background: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited.

Methods: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.

Differential Role of G Protein-Coupled Receptor Kinase 5 in Physiological Versus Pathological Cardiac Hypertrophy.

Rationale: G protein-coupled receptor kinases (GRKs) are dynamic regulators of cellular signaling. GRK5 is highly expressed within myocardium and is upregulated in heart failure. Although GRK5 is a critical regulator of cardiac G protein-coupled receptor signaling, recent data has uncovered noncanonical activity of GRK5 within nuclei that plays a key role in pathological hypertrophy.

GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity.

Rationale: G protein-coupled receptor kinases (GRKs) acting in the cardiomyocyte regulate important signaling events that control cardiac function. Both GRK2 and GRK5, the predominant GRKs expressed in the heart, have been shown to be upregulated in failing human myocardium. Although the canonical role of GRKs is to desensitize G protein-coupled receptors via phosphorylation, it has been demonstrated that GRK5, unlike GRK2, can reside in the nucleus of myocytes and exert G protein-coupled receptor-independent effects that promote maladaptive cardiac hypertrophy and heart failure.

In vitro regulation of ACTH release from neurointermediate lobe of rat hypophysis. III. Effect of potassium (K+), calcium (Ca++) and dibutyryl cyclic 3',5'-adenosine monophosphate (dbc-AMP).

Alterations in the ionic composition of the medium and different secretagogues have been used in order to study the mechanism of release of ACTH from superfused neurointermediate lobes (NIL) of rat hypophysis. We showed that: (a) a tenfold increase of K+ in the medium caused a reversible and repeatable stimulation of the ACTH release; (b) removal of Ca++ reversibly abolished the stimulating effect of high K+; (c) removal of Ca++ had no effect on the stimulating effect of a hypothalamic extract (HE); (d) in the latter case, a reversible significant weakening was obtained by the addition of EDTA in the Ca++-free medium; (e) dbc-AMP caused a reversible and repeatable stimulation of the ACTH release; (f) comparable results were obtained for anterior lobes (AL) superfused in the same conditions. From these data we can conclude that Ca++ is necessary for the stimulation of the hormonal release and that factors such as K+ or dbc-AMP can mimic the in vitro stimulating effect of a HE.