Nuclear Type I Myosins are Essential for Life and Genome Organization.

The active transport of large biomolecules within a cell is critical for homeostasis. While the cytoplasmic process is well-studied, how the spacing of nucleoplasmic cargo is coordinated is poorly understood. We investigated the impact of myosin motors in the nucleus of budding yeast.

The conceptus and its parts: ontogenetic recapitulation in early human development.

Our understanding of the processes of human development that occur during and just after implantation is still incomplete. The anatomical studies by Erich Blechschmidt (1904-1992) at the University of Göttingen demonstrate the uniqueness and beauty of the early stages of individual human development or ontogeny. The interpretations of human embryology by Blechschmidt offer a simple unifying hypothesis: metabolic and biomechanical events are repeated, and this can be described as an ontogenetic recapitulation.

Use of a SC5314 PacBio HiFi reads dataset to close gaps in the reference genome assembly, reveal a subtelomeric gene family, and produce accurate phased allelic sequences.

SC5314 is the most-often used strain for molecular manipulation of the species. The SC5314 reference genome sequence is the result of considerable effort from many scientists and has advanced research into fungal biology and pathogenesis. Although the resource is highly developed and presented in a phased diploid format, the sequence includes gaps and does not extend to the telomeres on its eight chromosome pairs.

Establishing Order Through Disorder by the Hsp90 Molecular Chaperone.

The Heat Shock Protein 90 (Hsp90) molecular chaperone is a key driver of protein homeostasis (proteostasis) under physiologically normal and stress conditions. In eukaryotes, Hsp90 is essential and is one of the most abundant proteins in a cell where the chaperone shuttles between the cytoplasm and nucleus to fold, stabilize, and regulate client proteins and protein complexes. Numerous high-throughput screens have mapped the Hsp90 interactome, building a vast network comprising ∼25% of the proteome in budding yeast.

Protocol for establishing a protein interactome based on close physical proximity to a target protein within live budding yeast.

Here, we present a protocol for establishing a protein interactome based on close physical proximity to a target protein within live yeast cells. We describe steps for capturing both transient and stable binders by integrating a non-natural amino acid. We detail procedures for employing a site-directed method for labeling the surface that mediates protein associations and uncovers the binding sites on the interactors.

An improved NRRL YB-4239 genome assembly substantiated by its electrophoretic karyotype.

Pacific Biosciences long-read sequencing was used to improve the genome assembly for strain NRRL YB-4239 (ATCC 11503). The new assembly included eight chromosomes that were substantiated by the electrophoretic karyotype. The nuclear genome was 16.

The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions.

Molecular chaperones govern proteome health to support cell homeostasis. An essential eukaryotic component of the chaperone system is Hsp90. Using a chemical-biology approach, we characterized the features driving the Hsp90 physical interactome.

An Environmental Scan of Advanced Practice Radiation Therapy in the United States: A PESTEL Analysis.

Purpose: In 2021, the Advanced Practice Radiation Therapy Working Group (APRTWG) was established in the United States as a grassroots alliance of multidisciplinary radiation oncology professionals-radiation therapists, physicians, dosimetrists, and administrators-located across the country, interested in studying and establishing the Advanced Practice Radiation Therapist (APRT) level of practice in the United States. The APRT model has shown success in the United Kingdom, Canada, Australia, Singapore, and other countries, documenting the value of the APRT to the quality and advancement of clinical care. In the United States, the APRTWG seeks to coordinate activities, align resources, and drive the national agenda to collectively develop and define novel models of care using APRT in line with the evolving needs of patients and the radiation therapy profession.

Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022.

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones.

Prehospital Cardiovascular Autoregulatory Disturbances Correlate With the Functional Neuroanatomy of Acute Spinal Cord Injury.

Study Design: Retrospective study.

Objective: The importance of attenuating the cardiovascular autoregulatory disturbances accompanying acute spinal cord injury (SCI) has long been recognized. This report assembles SCI emergency service data and correlates cardiovascular parameters to preserved functional neuroanatomy.

Survival Model of Thoracic Contusion Spinal Cord Injury in the Domestic Pig.

Spinal cord injury (SCI) frequently results in motor, sensory, and autonomic dysfunction for which there is currently no cure. Recent pre-clinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and may assist the translation of potential therapeutic interventions.

The Transcription Factor YY-1 Is an Essential Regulator of T Follicular Helper Cell Differentiation.

T follicular helper (T) cells are a specialized subset of CD4 T cells that deliver critical help signals to B cells for the production of high-affinity Abs. Understanding the genetic program regulating T differentiation is critical if one wants to manipulate T cells during vaccination. A large number of transcription factor (TFs) involved in the regulation of T differentiation have been characterized.

Regulation of Protein Transport Pathways by the Cytosolic Hsp90s.

The highly conserved molecular chaperone heat shock protein 90 (Hsp90) is well-known for maintaining metastable proteins and mediating various aspects of intracellular protein dynamics. Intriguingly, high-throughput interactome studies suggest that Hsp90 is associated with a variety of other pathways. Here, we will highlight the potential impact of Hsp90 in protein transport.

Persistently Raised Serum Titanium Levels After Spinal Instrumentation in Children.

Study Design: Prospective study of patients undergoing elective spinal deformity surgery with repeated testing for circulating metal ions including preoperative levels acting as controls.

Objective: The aim was to determine if levels of particular circulating metal ions are maintained to two years postsurgery including different implant systems and rods.

Summary Of Background Data: Adults having hip replacements, especially metal-on-metal bearings, may develop high metal ion levels.

Acute Cytomegalovirus Illness in an Immunocompetent Adult Causing Intravascular Hemolysis and Suspected Hemophagocytic Lymphohistiocytosis.

Background: Primary cytomegalovirus (CMV) infection of the immunocompetent host usually produces little-to-no illness. Occasionally, the infection results in mononucleosis syndrome, protracted fever, hepatitis, tissue-invasive disease, or Guillain-Barré syndrome. Hemolytic anemia and hemophagocytic lymphohistiocytosis (HLH) are rare complications that have not been reported to co-occur.

Inhibiting U1 telescripting: A means to an end for transcription.

In this issue of Molecular Cell, Cugusi et al. (2022) discover that inhibition of U1 telescripting is a novel mechanism that promotes a switch between gene programs in response to heat stress.

Ethical questions arising from Otfrid Foerster's use of the Sherrington method to map human dermatomes.

Otfrid Foerster (1873-1941) is well known for his maps of human dermatomes. We have examined the history of the development of his protocols for mapping dermatomes by analyzing his lectures and publications from 1908 to 1939, focusing on his Schorstein Memorial Lecture in 1932 and his use of the isolation (Sherrington) method, in which a single dorsal root is spared in a sequence of resections (dorsal rhizotomies). Because of the absence of medical records for Foerster's patients, we also review eyewitness accounts of his operating technique, his occasional comments on patients, and the issue of consent.

A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.

Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP).

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice.

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout () mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of mice.

Local Bone Grafting Is Sufficient for Instrumented Adolescent Idiopathic Scoliosis Surgery: A Preliminary Study.

Background: Several options for grafting exist; iliac crest bone grafting, allografts, and bone substitutes. Local bone graft (LBG) offers high-quality bone graft and no commercial cost. The aim of this study was to assess the clinical and radiologic results of adolescent idiopathic scoliosis (AIS) surgery with posterior instrumentation and fusion (PIF) in patients using only LBG and to measure the quantities harvested.