Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription.

Histone Deacetylase 1 (HDAC1) removes acetyl groups from lysine residues on core histones, a critical step in regulating chromatin accessibility. Despite histone deacetylation being an apparently repressive activity, suppression of HDACs causes both up- and downregulation of gene expression. Here we exploited the degradation tag (dTAG) system to rapidly degrade HDAC1 in mouse embryonic stem cells (ESCs) lacking its paralog, HDAC2.

FAM81A is a postsynaptic protein that regulates the condensation of postsynaptic proteins via liquid-liquid phase separation.

Proteome analyses of the postsynaptic density (PSD), a proteinaceous specialization beneath the postsynaptic membrane of excitatory synapses, have identified several thousands of proteins. While proteins with predictable functions have been well studied, functionally uncharacterized proteins are mostly overlooked. In this study, we conducted a comprehensive meta-analysis of 35 PSD proteome datasets, encompassing a total of 5,869 proteins.

Decision-making processes in image guided radiotherapy: A think aloud study.

Introduction: 3D Image Guided Radiotherapy (IGRT) using Cone Beam Computer Tomography (CBCT) has been implemented for a range of treatment sites across the UK in the last decade. A paucity of evidence exists to understand how radiation therapists (RTTs) make clinical decisions during image interpretation as part of the IGRT process. The aim of this study was to investigate the decision-making processes used by RTTs during image interpretation of IGRT.

Typhoid toxin hijacks Wnt5a to establish host senescence and Salmonella infection.

Damage to our genome causes acute senescence in mammalian cells, which undergo growth arrest and release a senescence-associated secretory phenotype (SASP) that propagates the stress response to bystander cells. Thus, acute senescence is a powerful tumor suppressor. Salmonella enterica hijacks senescence through its typhoid toxin, which usurps unidentified factors in the stress secretome of senescent cells to mediate intracellular infections.

Retrospective evaluation of MRI findings in arthroscopically confirmed cases of hypermobile lateral meniscus.

Objective: To identify preoperative MRI findings in patients with arthroscopically confirmed hypermobile lateral meniscus utilizing a standard MRI knee protocol, with comparison to normal control and lateral meniscal tear groups.

Subjects And Methods: All patients with arthroscopically confirmed hypermobile lateral meniscus diagnosed at our institution were retrospectively identified. The following structures were evaluated on preoperative knee MRIs: superior and inferior popliteomeniscal fascicles, lateral meniscus and meniscocapsular junction, popliteal hiatus, and soft tissue edema around the popliteal hiatus.

Utility of preoperative MRI for assessing proximal fragment vascularity in scaphoid nonunion.

Aims: The benefit of MRI in the preoperative assessment of scaphoid proximal fragment vascularity remains controversial. The purpose of this study is to compare preoperative MRI findings to intraoperative bleeding of the proximal scaphoid.

Methods: A retrospective review of 102 patients who underwent surgery for scaphoid nonunion between January 2000 and December 2020 at a single institution were identified.

Outcomes in patients with clinically suspected pedal osteomyelitis based on bone marrow signal pattern on MRI.

: confluent T1 hypointense marrow signal is widely accepted to represent osteomyelitis on MRI. Some authors have suggested that non-confluent bone marrow signal abnormality should be considered early osteomyelitis. The purpose of this study was to address this issue by comparing the rate of osteomyelitis and amputation based on T1 marrow signal characteristics.

A potential histone-chaperone activity for the MIER1 histone deacetylase complex.

Histone deacetylases 1 and 2 (HDAC1/2) serve as the catalytic subunit of six distinct families of nuclear complexes. These complexes repress gene transcription through removing acetyl groups from lysine residues in histone tails. In addition to the deacetylase subunit, these complexes typically contain transcription factor and/or chromatin binding activities.

Sec22b is a critical and nonredundant regulator of plasma cell maintenance.

Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Sec22b as a unique and critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced.

Radiation therapist perceptions on how artificial intelligence may affect their role and practice.

Introduction: The use of artificial intelligence (AI) has increased in medical radiation science, with advanced computing and modelling. Considering radiation therapists (RTs) perceptions of how this may affect their role is imperative, as this will contribute to increasing the efficiency of implementation and improve service delivery.

Methods: A peer-reviewed anonymous survey was developed and completed by 105 RTs between April and June 2021.

Advantages of CT Versus MRI for Preoperative Assessment of Osteochondritis Dissecans of the Capitellum.

Background: Magnetic resonance imaging (MRI) is considered to be the gold standard for imaging of osteochondritis dissecans (OCD).

Purpose/hypothesis: The purpose was to determine the additional value of a preoperative computed tomography (CT) scan in adolescent patients with capitellar OCD of the elbow. Consistent with the fact that OCD is a lesion involving the subchondral bone, the hypothesis was that CT would be superior to MRI for imaging OCD of the capitellum.

The EGFR/ErbB inhibitor neratinib modifies the neutrophil phosphoproteome and promotes apoptosis and clearance by airway macrophages.

Dysregulated neutrophilic inflammation can be highly destructive in chronic inflammatory diseases due to prolonged neutrophil lifespan and continual release of histotoxic mediators in inflamed tissues. Therapeutic induction of neutrophil apoptosis, an immunologically silent form of cell death, may be beneficial in these diseases, provided that the apoptotic neutrophils are efficiently cleared from the tissue. Previous research in our group identified ErbB inhibitors as able to induce neutrophil apoptosis and reduce neutrophilic inflammation both and .

Multimodality evaluation of transfascial muscle and other soft tissue herniations of the extremities.

This review illustrates the multimodality assessment of transfascial muscle and other soft tissue herniations of the extremities. Transfascial herniations of the extremities can develop from congenital or acquired disruptions of the deep fascia, resulting in herniation of the underlying muscle, nerve, or soft tissue tumor into the subcutaneous tissues. While most patients present with a painless subcutaneous nodule that may change in size with muscle activation, some may experience focal or diffuse extremity symptoms such as pain and paresthesias.

Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections.

B.1.1.

Developmental disruption to the cortical transcriptome and synaptosome in a model of SETD1A loss-of-function.

Large-scale genomic studies of schizophrenia implicate genes involved in the epigenetic regulation of transcription by histone methylation and genes encoding components of the synapse. However, the interactions between these pathways in conferring risk to psychiatric illness are unknown. Loss-of-function (LoF) mutations in the gene encoding histone methyltransferase, SETD1A, confer substantial risk to schizophrenia.

Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants.

Coordinated programs of gene expression drive brain development. It is unclear which transcriptional programs, in which cell-types, are affected in neuropsychiatric disorders such as schizophrenia. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons.

A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults.

Background: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4.

Medial patellofemoral ligament MRI abnormalities in the setting of MCL injuries: are they clinically relevant?

Objective: To assess MRI abnormalities of the medial patellofemoral ligament (MPFL) in patients with clinically and MRI-proven superficial medial collateral ligament (sMCL) injuries and determine the clinical significance.

Materials And Methods: High-field strength knee MRI examinations were selected which demonstrated sMCL injuries. These cases were retrospectively reviewed for the presence, location, and severity of MPFL abnormality.

Proximity-dependent biotin identification (BioID) reveals a dynamic LSD1-CoREST interactome during embryonic stem cell differentiation.

Lysine specific demethylase 1 (LSD1) regulates gene expression as part of the CoREST complex, along with co-repressor of REST (CoREST) and histone deacetylase 1 (HDAC1). CoREST is recruited to specific genomic loci by core components and numerous transient interactions with chromatin-associated factors and transcription factors. We hypothesise that many of these weaker and transient associations may be difficult to identify using traditional co-immunoprecipitation methods.