Myosin dilated cardiomyopathy mutation S532P disrupts actomyosin interactions, leading to altered muscle kinetics, reduced locomotion, and cardiac dilation in .

Dilated cardiomyopathy (DCM), a life-threatening disease characterized by pathological heart enlargement, can be caused by myosin mutations that reduce contractile function. To better define the mechanistic basis of this disease, we employed the powerful genetic and integrative approaches available in To this end, we generated and analyzed the first fly model of human myosin-induced DCM. The model reproduces the S532P human β-cardiac myosin heavy chain DCM mutation, which is located within an actin-binding region of the motor domain.

On-demand biomanufacturing of protective conjugate vaccines.

Conjugate vaccines are among the most effective methods for preventing bacterial infections. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. To address these limitations, we developed a modular technology for in vitro conjugate vaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenic Upon rehydration, iVAX reactions synthesize clinically relevant doses of conjugate vaccines against diverse bacterial pathogens in 1 hour.

Alternative N-terminal regions of myosin heavy chain II regulate communication of the purine binding loop with the essential light chain.

We investigated the biochemical and biophysical properties of one of the four alternative exon-encoded regions within the myosin catalytic domain. This region is encoded by alternative exons 3a and 3b and includes part of the N-terminal β-barrel. Chimeric myosin constructs (IFI-3a and EMB-3b) were generated by exchanging the exon 3-encoded areas between native slow embryonic body wall (EMB) and fast indirect flight muscle myosin isoforms (IFI).

Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism.

Background: Distal arthrogryposis (DA) is a group of autosomal dominant skeletal muscle diseases characterized by congenital contractures of distal limb joints. The most common cause of DA is a mutation of the embryonic myosin heavy chain gene, MYH3. Human phenotypes of DA are divided into the weakest form-DA1, a moderately severe form-DA2B (Sheldon-Hall Syndrome), and a severe DA disorder-DA2A (Freeman-Sheldon Syndrome).

Clinical improvement of severe COVID-19 pneumonia in a pregnant patient after caesarean delivery.

The clinical implications of COVID-19 in pregnancy remain unknown. While preliminary reports demonstrate that pregnant patients have a similar symptomatic presentation to the general population, the appropriate management and timing of delivery in these patients is still unclear, as pregnancy may impose additional risk factors and impede recovery in gravid patients. In this brief report, we present a case of COVID-19 in a pregnant patient with severe respiratory compromise, whose clinical status significantly improved after caesarean delivery.

Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction in Drosophila models of myosin-based Freeman-Sheldon syndrome.

Using Drosophila melanogaster, we created the first animal models for myosin-based Freeman-Sheldon syndrome (FSS), a dominant form of distal arthrogryposis defined by congenital facial and distal skeletal muscle contractures. Electron microscopy of homozygous mutant indirect flight muscles showed normal (Y583S) or altered (T178I, R672C) myofibril assembly followed by progressive disruption of the myofilament lattice. In contrast, all alleles permitted normal myofibril assembly in the heterozygous state but caused myofibrillar disruption during aging.

Author Correction: Single-pot glycoprotein biosynthesis using a cell-free transcription-translation system enriched with glycosylation machinery.

The original version of this Article contained an error in Figure 2, wherein the bottom right western blot panel in Figure 2a was blank. This has now been corrected in both the PDF and HTML versions of the Article.

BioBits™ Bright: A fluorescent synthetic biology education kit.

Synthetic biology offers opportunities for experiential educational activities at the intersection of the life sciences, engineering, and design. However, implementation of hands-on biology activities in classrooms is challenging because of the need for specialized equipment and expertise to grow living cells. We present BioBits™ Bright, a shelf-stable, just-add-water synthetic biology education kit with easy visual outputs enabled by expression of fluorescent proteins in freeze-dried, cell-free reactions.

BioBits™ Explorer: A modular synthetic biology education kit.

Hands-on demonstrations greatly enhance the teaching of science, technology, engineering, and mathematics (STEM) concepts and foster engagement and exploration in the sciences. While numerous chemistry and physics classroom demonstrations exist, few biology demonstrations are practical and accessible due to the challenges and concerns of growing living cells in classrooms. We introduce BioBits™ Explorer, a synthetic biology educational kit based on shelf-stable, freeze-dried, cell-free (FD-CF) reactions, which are activated by simply adding water.

Single-pot glycoprotein biosynthesis using a cell-free transcription-translation system enriched with glycosylation machinery.

The emerging discipline of bacterial glycoengineering has made it possible to produce designer glycans and glycoconjugates for use as vaccines and therapeutics. Unfortunately, cell-based production of homogeneous glycoproteins remains a significant challenge due to cell viability constraints and the inability to control glycosylation components at precise ratios in vivo. To address these challenges, we describe a novel cell-free glycoprotein synthesis (CFGpS) technology that seamlessly integrates protein biosynthesis with asparagine-linked protein glycosylation.

Inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains.

Active participation of endogenous retroviruses (ERVs) in disease processes has been exemplified by the finding that the HERV (human ERV)-W envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We also demonstrated that injury-elicited stressors alter the expression of murine ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to stress (e.

Titin strain contributes to the Frank-Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins.

The Frank-Starling mechanism of the heart is due, in part, to modulation of myofilament Ca(2+) sensitivity by sarcomere length (SL) [length-dependent activation (LDA)]. The molecular mechanism(s) that underlie LDA are unknown. Recent evidence has implicated the giant protein titin in this cellular process, possibly by positioning the myosin head closer to actin.

ERE database: a database of genomic maps and biological properties of endogenous retroviral elements in the C57BL/6J mouse genome.

Endogenous retroviral elements (EREs), a family of transposable elements, constitute a substantial fraction of mammalian genomes. It is expected that profiles of the ERE sequences and their genomic locations are unique for each individual. Comprehensive characterization of the EREs' genomic locations and their biological properties is essential for understanding their roles in the pathophysiology of the host.

Identification of a unique library of complex, but ordered, arrays of repetitive elements in the human genome and implication of their potential involvement in pathobiology.

Approximately 2% of the human genome is reported to be occupied by genes. Various forms of repetitive elements (REs), both characterized and uncharacterized, are presumed to make up the vast majority of the rest of the genomes of human and other species. In conjunction with a comprehensive annotation of genes, information regarding components of genome biology, such as gene polymorphisms, non-coding RNAs, and certain REs, is found in human genome databases.

Post-injury stress signals alter epigenetic profile of cytosine methylation in the proviral genome of endogenous retroviruses.

The majority of epigenetic methylation events at cytosine residues of the genome are reported to occur in transposable elements, as a result, it contributes to genome stability by repressing their transposition activity. Our recent studies demonstrated that the expression of certain murine endogenous retroviruses (MuERVs), a family of retrotransposons, is modulated in the liver after burn injury and sepsis. In this study, we investigated whether burn-elicited stress signals alter epigenetic methylation profile of cytosine residues of the MuERV proviral genome.

Identification of putative endogenous retroviruses actively transcribed in the brain.

Remnant proviral sequences in the genome resulting from the ancient germline infection of exogenous retroviruses are called endogenous retroviruses (ERVs). The transcriptional activation of human ERVs (HERVs) in the brain of patients with some neurologic diseases suggests that ERVs may participate in certain disease processes in the central nervous system. In this study, we identified putative murine ERVs (MuERVs) which are transcriptionally active in the brain and characterized their biological properties to better understand the ERVs' roles in the brain pathophysiology.

Cosegregation of CD14 locus and polymorphic alleles of glucocorticoid receptor and protocadherins into CD14 knockout mouse genome.

Targeted mutagenesis technology has been used to investigate the biological characteristics of genes. We incidentally observed a discrepancy in the size of the glucocorticoid receptor (GCR) between CD14 knockout (KO) mice and backcross controls. The CD14 KO mice were generated using 129S4/SvJae-derived J1 embryonic stem cells, C57BL/ 6J donor blastocysts, and C57BL/6J backcross strain.

First-trimester C-reactive protein and subsequent gestational diabetes.

Objective: Systemic inflammation is associated with the development of type 2 diabetes. We tested the hypothesis that increased inflammation, measured early in pregnancy, is associated with the subsequent development of gestational diabetes mellitus (GDM), a precursor of type 2 diabetes.

Research Design And Methods: We conducted a prospective nested case-control study in a pregnancy cohort.

First trimester insulin resistance and subsequent preeclampsia: a prospective study.

Insulin resistance is implicated in the pathogenesis of preeclampsia, but prospective data are limited. SHBG, a marker of insulin resistance among nonpregnant individuals, has not been studied in detail during pregnancy. We conducted a prospective, nested, case-control study to test the hypothesis that increased insulin resistance, marked by reduced first trimester SHBG levels, is associated with increased risk of subsequent preeclampsia.