Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer's core components VPS26, VPS29, and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane.

The Protective Effect of IL-17A in Pneumonic Plague Can Be Compensated by Effective Vaccines and Immunization Strategies in Mice.

Plague, caused by , poses a public health threat not only due to sporadic outbreaks across the globe but also due to its potential as a biothreat agent. Ironically, among the seven deadliest pandemics in global history, three were caused by . Pneumonic plague, the more contagious and severe form of the disease, is difficult to contain, requiring either prophylactic antibiotic treatment or vaccination.

Independence of Centromeric and Pericentromeric Chromatin Stability on CCAN Components.

The chromatin of the centromere provides the assembly site for the mitotic kinetochore that couples microtubule attachment and force production to chromosome movement in mitosis. The chromatin of the centromere is specified by nucleosomes containing the histone H3 variant CENP-A. The constitutive centromeric-associated network (CCAN) and kinetochore are assembled on CENP-A chromatin to enable chromosome separation.

ATG9A facilitates the closure of mammalian autophagosomes.

Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite for its subsequent fusion with endolysosomal organelles and degradation of the sequestered cargo. ATG9A, a key integral membrane protein of the autophagy pathway, is best known for its role in the formation and expansion of phagophores.

Combination of live attenuated and adenovirus-based vaccines completely protects interferon gamma (IFNγ) knockout mice against pneumonic plague.

Two live attenuated vaccines (LAVs), LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their efficacy and immune responses in wild type (WT) and interferon gamma (IFNγ) knockout (KO) mice in a C57BL/6 background. While LMA and LMP are triple deletion mutants of CO92 strain, Ad5-YFV incorporates three protective plague immunogens. An impressive 80-100% protection was observed in all vaccinated animals against highly lethal intranasal challenge doses of parental CO92.

Qualitative Study of Health Care Team Perception of the Benefits and Limitations of Remote Symptom Monitoring.

Purpose: Remote symptom monitoring (RSM) using electronic patient-reported outcomes (ePROS) connects patients and health care teams between appointments. Patient-perceived benefits and drawbacks of RSM are well-known, but health care team members' perceptions are less clear.

Methods: Health care team members from the University of Alabama at Birmingham and the University of South Alabama Health Mitchell Cancer Institute participated in semi-structured qualitative interviews to explore their experiences and perspectives on RSM benefits and limitations.

Federal Cervical Cancer Collaborative: Improving cervical cancer prevention through vaccination, screening, and management in safety-net settings of care.

The Federal Cervical Cancer Collaborative (FCCC) was established by the Health Resources and Services Administration Office of Women's Health and its interagency partners within the U.S. Department of Health and Human Services.

Patient-Perceived Benefits and Limitations of Standard of Care Remote Symptom Monitoring During Cancer Treatment.

Introduction: Remote symptom monitoring (RSM) allows patients to electronically self-report symptoms to their healthcare team for individual management. Clinical trials have demonstrated overarching benefits; however, little is known regarding patient-perceived benefits and limitations of RSM programs used during patient care.

Methods: This prospective qualitative study from December 2021 to May 2023 included patients with cancer participating in standard-of-care RSM at the University of Alabama at Birmingham (UAB) in Birmingham, AL, and the Univeristy of South Alabama (USA) Health Mitchell Cancer Institute (MCI) in Mobile, AL.

Survivor Health Connection Project: Understanding Experiences of Accessing Health Care Among Those Affected by Intimate Partner Violence During the COVID-19 Pandemic.

Objectives: Intimate partner violence (IPV) has short- and long-term health effects, including physical injuries and traumatic brain injury, as well as sexual, reproductive, and mental health issues. However, accessing necessary health care is often challenging for IPV survivors and became even more difficult during the COVID-19 pandemic. We examined access to health care among those affected by IPV during the COVID-19 pandemic to better connect survivors to health and social support services.

Utilizing AfDesign for Developing a Small Molecule Inhibitor of PICK 1-PDZ.

Introduction: The PICK1 PDZ domain has been identified as a potential drug target for neurological disorders. After many years of effort, a few inhibitors, such as TAT-C5 and mPD5, have been discovered experimentally to bind to the PDZ domain with a relatively high binding affinity. With the rapid growth of computational research, there is an urgent need for more efficient computational methods to design viable ligands that target proteins.

Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here we show that ATG5 associates with retromer's core components VPS26, VPS29 and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane.

Regulatory T cells as a possible new target in epilepsy?

Epilepsy is a complex chronic brain disorder with diverse clinical features that can be caused by various triggering events, such as infections, head trauma, or stroke. During epileptogenesis, various abnormalities are observed, such as altered cellular homeostasis, imbalance of neurotransmitters, tissue changes, and the release of inflammatory mediators, which in combination lead to spontaneous recurrent seizures. Regulatory T cells (Tregs), a subtype of CD4Foxp3 T cells, best known for their key function in immune suppression, also seem to play a role in attenuating neurodegeneration and suppressing pathological inflammation in several brain disease states.

Assessing the association between quantity and quality of family caregiver participation in decision-making clinical encounters on patient activation in the metastatic breast cancer setting.

Objective: Caregivers support individuals undergoing cancer treatment by assisting with activities, managing care, navigating healthcare systems, and communicating with care teams. We explored the quality and quantity of caregiver participation during recorded decision-making clinical appointments in women with metastatic breast cancer.

Methods: This was a convergent parallel mixed methods study that utilized qualitative and quantitative data collection and analysis.

A Bacteriophage Cocktail Targeting Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model.

, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug resistant strains. The dissemination of such strains could be catastrophic, with public health consequences far more daunting than those caused by the recent COVID-19 pandemic.

Assessing the Impact of Family Caregivers in Clinical Encounter Participation on Patient Activation in the Metastatic Breast Cancer Setting.

Objective: Caregivers support individuals undergoing cancer treatment by assisting with activities, managing care, navigating healthcare systems, and communicating with care teams. We explored the quantity and quality of caregiver participation during recorded clinical appointments in women with metastatic breast cancer.

Methods: This was a convergent parallel mixed methods study.

AlphaFold Accurately Predicts the Structure of Ribosomally Synthesized and Post-Translationally Modified Peptide Biosynthetic Enzymes.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products biosynthesized from a genetically encoded precursor peptide. The enzymes that install the post-translational modifications on these peptides have the potential to be useful catalysts in the production of natural-product-like compounds and can install non-proteogenic amino acids in peptides and proteins. However, engineering these enzymes has been somewhat limited, due in part to limited structural information on enzymes in the same families that nonetheless exhibit different substrate selectivities.

Mammalian ATG8 proteins maintain autophagosomal membrane integrity through ESCRTs.

The canonical autophagy pathway in mammalian cells sequesters diverse cytoplasmic cargo within the double membrane autophagosomes that eventually convert into degradative compartments via fusion with endolysosomal intermediates. Here, we report that autophagosomal membranes show permeability in cells lacking principal ATG8 proteins (mATG8s) and are unable to mature into autolysosomes. Using a combination of methods including a novel in vitro assay to measure membrane sealing, we uncovered a previously unappreciated function of mATG8s to maintain autophagosomal membranes in a sealed state.

Inactivation of DRG1, encoding a translation factor GTPase, causes a recessive neurodevelopmental disorder.

Purpose: Developmentally regulated Guanosine-5'-triphosphate-binding protein 1 (DRG1) is a highly conserved member of a class of GTPases implicated in translation. Although the expression of mammalian DRG1 is elevated in the central nervous system during development, and its function has been implicated in fundamental cellular processes, no pathogenic germline variants have yet been identified. Here, we characterize the clinical and biochemical consequences of DRG1 variants.

"": Health Care Provider Perceptions of the Effects of COVID-19 on Intimate Partner Violence.

This study sought to understand the effects of COVID-19, including movement-related restrictions such as shelter-in-place, quarantine, and isolation orders, on intimate partner violence (IPV) from the perspective of health care providers (HCPs) working at a public hospital in Atlanta, Georgia. From November 2020 to May 2021, we conducted 12 interviews. Three themes emerged: (1) HCPs perceived that COVID-19 movement-related restrictions likely exacerbated IPV; (2) HCPs encountered many practice-oriented and community barriers in IPV care provision during COVID-19; and (3) HCPs suggested process and partnership improvements for IPV response.

Simple and Effective Conformational Sampling Strategy for Intrinsically Disordered Proteins Using the UNRES Web Server.

Intrinsically disordered proteins (IDPs) contain more charged amino acids than folded proteins, resulting in a lack of hydrophobic core(s) and a tendency to adopt rapidly interconverting structures rather than well-defined structures. The structural heterogeneity of IDPs, encoded by the amino acid sequence, is closely related to their unique roles in biological pathways, which require them to interact with different binding partners. Recently, Robustelli and co-workers have demonstrated that a balanced all-atom force field can be used to sample heterogeneous structures of disordered proteins ( 2018, 115, E4758-E4766).

Impaired protein hydroxylase activity causes replication stress and developmental abnormalities in humans.

Although protein hydroxylation is a relatively poorly characterized posttranslational modification, it has received significant recent attention following seminal work uncovering its role in oxygen sensing and hypoxia biology. Although the fundamental importance of protein hydroxylases in biology is becoming clear, the biochemical targets and cellular functions often remain enigmatic. JMJD5 is a "JmjC-only" protein hydroxylase that is essential for murine embryonic development and viability.

Evaluation of the perioperative analgesic effects of grapiprant compared with carprofen in dogs undergoing elective ovariohysterectomy.

Objective: To evaluate and compare postoperative analgesic effects of grapiprant and carprofen in dogs undergoing ovariohysterectomy.

Animals: 42 sexually intact female healthy dogs (< 35 kg and 0.5 to 7 years old) were enrolled.

Correction: Gajurel et al. Production and Secretion of Isowighteone in Hairy Root Cultures of Pigeon Pea () Co-Treated with Multiple Elicitors. 2022, , 834.

In the original publication [...