The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy.

Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had an antitumoral effect in SM1 melanoma and CT26 colon cancer models and increased the efficacy of anti-programmed cell death protein 1 treatment, leading to complete remission in melanoma and increased response in colon cancer. AVS100 treatment increased pro-inflammatory tumor-infiltrating macrophages and CD8 effector T cells with an inflammatory and T cell effector gene signature.

Whole-genome bisulfite sequencing data analysis learning module on Google Cloud Platform.

This study describes the development of a resource module that is part of a learning platform named 'NIGMS Sandbox for Cloud-based Learning' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement.

A cloud-based learning module for biomarker discovery.

This manuscript describes the development of a resource module that is part of a learning platform named "NIGMS Sandbox for Cloud-based Learning" https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement.

ScSNViz: a user-friendly toolset for visualization and analysis of Cell-Specific Expressed SNVs.

Motivation: Understanding genetic variation at the single-cell level is crucial for insights into cellular heterogeneity, clonal evolution, and gene expression regulation, but there is a scarcity of tools for visualizing and analyzing cell-level genetic variants.

Results: We introduce scSNViz, a comprehensive R-based toolset for visualization and analysis of cell-specific expressed Single Nucleotide Variants (sceSNVs) within cell-barcoded single-cell RNA-sequencing (scRNA-seq) data. ScSNViz offers 3D sceSNV visualization capabilities for dimensionally reduced scRNA-seq gene expression data, compatibility with popular scRNA-seq processing tools like Seurat, cell-type classification tools such as SingleR and scType, and trajectory inference computation using Slingshot.

Using a decision tree to predict the number of COVID cases: a tutorial for beginners.

This manuscript describes the development of a module that is part of a learning platform named "NIGMS Sandbox for Cloud-based Learning" https://github.com/NIGMS/NIGMS-Sandbox . The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement.

Rural-urban disparities in health outcomes, clinical care, health behaviors, and social determinants of health and an action-oriented, dynamic tool for visualizing them.

While rural-urban disparities in health and health outcomes have been demonstrated, because of their impact on (and intervenability to improve) health and health outcomes, we sought to examine cross-sectional and longitudinal inequities in health, clinical care, health behaviors, and social determinants of health (SDOH) between rural and non-rural counties in the pre-pandemic era (2015 to 2019), and to present a Health Equity Dashboard that can be used by policymakers and researchers to facilitate examining such disparities. Therefore, using data obtained from 2015-2022 County Health Rankings datasets, we used analysis of variance to examine differences in 33 county level attributes between rural and non-rural counties, calculated the change in values for each measure between 2015 and 2019, determined whether rural-urban disparities had widened, and used those data to create a Health Equity Dashboard that displays county-level individual measures or compilations of them. We followed STROBE guidelines in writing the manuscript.

Evaluation and Management of Reduced Dietary Diversity in Children with Pediatric Feeding Disorder.

Pediatric Feeding Disorder, a common problem in children, is commoner in children with various developmental disorders. Children with pediatric feeding disorder can have food selectivity and lack dietary diversity (DD). In this paper, an understanding of DD in these children is provided along with a dietary diversity index that can be helpful in measuring and understanding the risks posed by this lack of DD.

Using Toolkits to Improve Students' Skills in Advocacy.

Background: Advocacy is widely recognized as a nursing responsibility. Speaking up, a form of advocacy, is known to benefit patient safety and quality of care yet research shows that nurses are hesitant to speak up and face multiple barriers when deciding to do so.

Method: A toolkit that included web-based learning modules and simulation experience with a standardized patient was developed to enhance advocacy skills in baccalaureate nursing students.

Evaluating and contextualizing the efficacy of portable HEPA filtration units in small exam rooms.

Background: Ambulatory clinics attend to COVID-19 patients, often in spaces with less than ideal ventilation. Testing and treatments can often include aerosol-generating procedures. Portable high efficiency particulate air (HEPA) filtration units have been used to remove airborne contaminants in these areas.

Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch.

Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires elaborate coordination of sensing and actuation mechanisms built into a single molecule. Here, we rationally designed a molecular switch that changes its subcellular localization in response to an intended stimulus such as an activator of protein kinase A (PKA).

A high-throughput predictive method for sequence-similar fold switchers.

Although most experimentally characterized proteins with similar sequences assume the same folds and perform similar functions, an increasing number of exceptions is emerging. One class of exceptions comprises sequence-similar fold switchers, whose secondary structures shift from α-helix <-> β-sheet through a small number of mutations, a sequence insertion, or a deletion. Predictive methods for identifying sequence-similar fold switchers are desirable because some are associated with disease and/or can perform different functions in cells.

Impact of a contactless prescription pickup kiosk on prescription abandonment, patient experience, and pharmacist consultations.

Objective: Investigate the impact of increased access to new and refilled prescriptions by means of an automated pickup kiosk (Asteres ScriptCenter) on prescription abandonment rates, patient experience, and pharmacist consultations.

Design: Nonrandomized, observational study using retrospective, deidentified data from the filling pharmacy, the kiosk, and a pharmacist-completed counseling documentation log over a 35-month study period.

Setting And Participants: Hospital employees opting to use a kiosk located in the lobby with 24 hours a day, 7 days a week access for pickups and a telephone pharmacist consultation service compared with employees using the regular counter at the filling pharmacy.

Functional and Regulatory Roles of Fold-Switching Proteins.

Fold-switching proteins respond to cellular stimuli by remodeling their secondary structures and changing their functions. Whereas several previous reviews have focused on various structural, physical-chemical, and evolutionary aspects of this newly emerging class of proteins, this minireview focuses on how fold switching modulates protein function and regulates biological processes. It first compares and contrasts fold switchers with other known types of proteins.

Rational Design of a Protein Kinase A Nuclear-cytosol Translocation Reporter.

Protein Kinase A (PKA) exists as a tetrameric holoenzyme which activates with increase of cAMP and plays an important role in many physiological processes including cardiac physiology, neuronal development, and adipocyte function. Although this kinase has been the subject of numerous biosensor designs, a single-fluorophore reporter that performs comparably to Förster resonance energy transfer (FRET) has not yet been reported. Here, we have used basic observations of electrostatic interactions in PKA substrate recognition mechanism and nucleus localization sequence motif to design a phosphorylation switch that shuttles between the cytosol and the nucleus, a strategy that should be generalizable to all basophilic kinases.

Learning-induced ribosomal RNA is required for memory consolidation in mice-Evidence of differentially expressed rRNA variants in learning and memory.

The transition from short-term to long-term forms of synaptic plasticity requires protein synthesis and new gene expression. Most efforts to understand experience-induced changes in neuronal gene expression have focused on the transcription products of RNA polymerase II-primarily mRNAs and the proteins they encode. We recently showed that nucleolar integrity and activity-dependent ribosomal RNA (rRNA) synthesis are essential for the maintenance of hippocampal long-term potentiation (LTP).

Cellular Application of Genetically Encoded Sensors and Impeders of AMPK.

Unraveling the spatiotemporal dynamics of 5'-AMP-activated protein kinase (AMPK) signaling is necessary to bridge the gap between nutrient signaling and downstream function. Three genetically encoded Förster Resonance Energy Transfer (FRET)-based AMPK biosensors are available yielding insight into how AMPK-derived signal propagates throughout a cell in response to particular inputs. These findings, together with accumulating evidence obtained from biochemical techniques, promise to give a holistic understanding of the AMPK signaling.

Correlational Study of Diabetic Retinopathy and Hearing Loss.

Purpose: Our research goal was to complete a retrospective chart review to determine if there is a correlation between the level of diabetic retinopathy and diabetic neurosensory hearing loss.

Methods: A retrospective analysis of 175 Department of Veterans Affairs Computerized Patient Record System charts was completed at the VA Portland Health Care System. Subjects were classified by degree of diabetic retinopathy as follows: no diabetic retinopathy (n = 80), mild nonproliferative diabetic retinopathy (n = 51), moderate nonproliferative diabetic retinopathy (n = 25), and combined severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (PDR) (n = 17).

Toward total synthesis of cell function: Reconstituting cell dynamics with synthetic biology.

Biological phenomena, such as cellular differentiation and phagocytosis, are fundamental processes that enable cells to fulfill important physiological roles in multicellular organisms. In the field of synthetic biology, the study of these behaviors relies on the use of a broad range of molecular tools that enable the real-time manipulation and measurement of key components in the underlying signaling pathways. This Review will focus on a subset of synthetic biology tools known as bottom-up techniques, which use technologies such as optogenetics and chemically induced dimerization to reconstitute cellular behavior in cells.

New ribosomes for new memories?

Widely thought to be a housekeeping process, the regulation and synthesis of rRNA emerges as a potentially central mechanism for the maintenance of synaptic plasticity and memory. We have recently shown that an essential component of late-phase synaptic plasticity is rRNA biosynthesis - the rate-limiting step in the production of new ribosomes. We hypothesize that a particular population of ribosomes is generated upon learning-associated neural activity to alter the rate of synthesis of plasticity factors at tagged synapses that will support the maintenance of synaptic plasticity and memory.

Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

Long-term memory (LTM) formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose) polymerase-1 (PARP-1), are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP) in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs.

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation.

Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide (2H2O) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover.

What is the value and impact of the safety World Conference? Evaluators' reflections of safety 2012.

Using survey and documentary information collected as part of an evaluation of the 2012 conference, this paper reflects upon the value of the 2012 World Conference to attendees of the event. The results are discussed in the context of questions about what the purpose of conference is to the world injury prevention community and how they are organised. The evaluators challenge the community and future organisers to clarify what the purpose of these events are to better inform future evaluation activities.

Regulation of acetylation restores proteolytic function of diseased myocardium in mouse and human.

Proteasome complexes play essential roles in maintaining cellular protein homeostasis and serve fundamental roles in cardiac function under normal and pathological conditions. A functional detriment in proteasomal activities has been recognized as a major contributor to the progression of cardiovascular diseases. Therefore, approaches to restore proteolytic function within the setting of the diseased myocardium would be of great clinical significance.