ProQ-associated small RNAs control motility in Vibrio cholerae.

Gene regulation at the post-transcriptional level is prevalent in all domains of life. In bacteria, ProQ-like proteins have emerged as important RNA chaperones facilitating RNA stability and RNA duplex formation. In the major human pathogen Vibrio cholerae, post-transcriptional gene regulation is key for virulence, biofilm formation, and antibiotic resistance, yet the role of ProQ has not been studied.

Coordination among cytoskeletal organization, cell contraction, and extracellular matrix development is dependent on LOX for aneurysm prevention.

Distinct and seemingly independent cellular pathways affecting intracellular machinery or extracellular matrix (ECM) deposition and organization have been implicated in aneurysm formation. One of the key genes associated with this pathology in both humans and mice is lysyl oxidase (LOX), a secreted ECM-modifying enzyme, highly expressed in medial vascular smooth muscle cells. To dissect the mechanisms leading to aneurysm development, we conditionally deleted Lox in smooth muscle cells.

Biological Insights from RNA-RNA Interactomes in Bacteria, as Revealed by RIL-seq.

Bacteria reside in constantly changing environments and require rapid and precise adjustments of gene expression to ensure survival. Small regulatory RNAs (sRNAs) are a crucial element that bacteria utilize to achieve this. sRNAs are short RNA molecules that modulate gene expression usually through base-pairing interactions with target RNAs, primarily mRNAs.

Diversification of molecular pattern recognition in bacterial NLR-like proteins.

Antiviral STANDs (Avs) are bacterial anti-phage proteins evolutionarily related to immune pattern recognition receptors of the NLR family. Type 2 Avs proteins (Avs2) were suggested to recognize the phage large terminase subunit as a signature of phage infection. Here, we show that Avs2 from Klebsiella pneumoniae (KpAvs2) can recognize several different phage proteins as signature for infection.

Reward system activation improves recovery from acute myocardial infarction.

Psychological processes have a crucial role in the recovery from acute myocardial infarction (AMI), yet the underlying mechanisms of these effects remain elusive. Here we demonstrate the impact of the reward system, a brain network associated with motivation and positive expectations, on the clinical outcomes of AMI in mice. Chemogenetic activation of dopaminergic neurons in the reward system improved the remodeling processes and vascularization after AMI, leading to enhanced cardiac performance compared to controls.

Induction of Superior Systemic and Mucosal Protective Immunity to SARS-CoV-2 by Nasal Administration of a VSV-ΔG-Spike Vaccine.

The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines' protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed to extend the longevity of vaccine protection, induce mucosal and systemic immunity and prevent viral transmission.

Evaluation of augmented reality training for a navigation device used for CT-guided needle placement.

Purpose: Numerous navigation devices for percutaneous, CT-guided interventions exist and are, due to their advantages, increasingly integrated into the clinical workflow. However, effective training methods to ensure safe usage are still lacking. This study compares the potential of an augmented reality (AR) training application with conventional instructions for the Cube Navigation System (CNS), hypothesizing enhanced training with AR, leading to safer clinical usage.

Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection.

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates.

Coordination between cytoskeletal organization, cell contraction and extracellular matrix development, is depended on LOX for aneurysm prevention.

Distinct, seemingly independent, cellular pathways affecting intracellular machineries or extracellular matrix (ECM) deposition and organization, have been implicated in aneurysm formation. One of the key genes associated with the pathology in both humans and mice is Lysyl oxidase (LOX), a secreted ECM-modifying enzyme, highly expressed in medial vascular smooth muscle cells. To dissect the mechanisms leading to aneurysm development, we conditionally deleted in smooth muscle cells.

Topical application of jojoba ( L.) wax enhances the synthesis of pro-collagen III and hyaluronic acid and reduces inflammation in the human skin organ culture model.

Jojoba ( L.) wax was previously reported to increase cutaneous wound healing, ameliorate acne and psoriasis manifestations, and reduce oxidative stress and inflammation. However, its potential cosmetic properties have not been fully investigated.

Pediatric COVID-19 Hospitalizations During the Omicron Surge.

Background: Treatment recommendations for children hospitalized with COVID-19 during the winter 2021-2022 omicron variant surge included remdesivir and dexamethasone for hypoxia and remdesivir for patients at risk of severe illness, including those with comorbidities. The omicron variant caused many otherwise-healthy children without hypoxia to be hospitalized for common viral syndromes like croup. This study aimed to characterize children hospitalized with COVID-19 during the omicron surge and describe their management and clinical trajectory.

Identification of T-Cell Epitopes Using a Combined In-Silico and Experimental Approach in a Mouse Model for SARS-CoV-2.

Following viral infection, T-cells are crucial for an effective immune response to intracellular pathogens, including respiratory viruses. During the COVID-19 pandemic, diverse assays were required in pre-clinical trials to evaluate the immune response following vaccination against SARS-CoV-2 and assess the response following exposure to the virus. To assess the nature and potency of the cellular response to infection or vaccination, a reliable and specific activity assay was needed.

σ-dependent small RNA regulation of flagella biosynthesis.

Flagella are important for bacterial motility as well as for pathogenesis. Synthesis of these structures is energy intensive and, while extensive transcriptional regulation has been described, little is known about the posttranscriptional regulation. Small RNAs (sRNAs) are widespread posttranscriptional regulators, most base pairing with mRNAs to affect their stability and/or translation.

Generation of recombinant mAbs to vaccinia virus displaying high affinity and potent neutralization.

Members of the genus can cause severe infections in humans. Global vaccination against smallpox, caused by the variola virus, resulted in the eradication of the disease in 1980. Shortly thereafter, vaccination was discontinued, and as a result, a large proportion of the current population is not protected against orthopoxviruses.

A conserved family of immune effectors cleaves cellular ATP upon viral infection.

During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. Here, we report a family of immune effectors in bacteria that, upon phage infection, degrade cellular adenosine triphosphate (ATP) and deoxyadenosine triphosphate (dATP) by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems, including cyclic oligonucleotide-based antiviral signaling systems (CBASS), prokaryotic argonautes, and nucleotide-binding leucine-rich repeat (NLR)-like proteins, and we show that ATP and dATP degradation during infection halts phage propagation.

A quality improvement initiative to improve folic acid supplementation counseling for adolescent females with epilepsy.

Objective: We designed a quality improvement (QI) project to improve rates of documented folic acid supplementation counseling for adolescent females with epilepsy, consistent with a quality measure from the American Academy of Neurology and American Epilepsy Society. Our SMART aim was to increase the percentage of visits at which folic acid counseling was addressed from our baseline rate of 23% to 50% by July 1, 2020.

Methods: This initiative was conducted in female patients ≥12 years old with epilepsy who were prescribed daily antiseizure medication and were seen by the 13 providers in our Neurology QI Program.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

Background: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings.

Methods: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021.

Bridging the "Know-Do" Gaps in Five Non-Communicable Diseases Using a Common Framework Driven by Implementation Science.

According to the United Nations High-Level Meeting 2018, five non-communicable diseases (NCDs) including cardiovascular diseases, chronic respiratory diseases, diabetes mellitus, cancer, and mental health conditions accounted for two-thirds of global deaths. These five NCDs share five common risk factors including tobacco use, unhealthy diets, physical inactivity, alcohol use, and air pollution. Low- and middle-income countries (LMICs) face larger burden of NCDs than high-income countries (HICs), due to differences in ecological, technological, socioeconomic and health system development.

VSV-ΔG-Spike Candidate Vaccine Induces Protective Immunity and Protects K18-hACE2 Mice against SARS-CoV-2 Variants.

Since the emergence of the original SARS-CoV-2, several variants were described, raising questions as to the ability of recently developed vaccine platforms to induce immunity and provide protection against these variants. Here, we utilized the K18-hACE2 mouse model to show that VSV-ΔG-spike vaccination provides protection against several SARS-CoV-2 variants: alpha, beta, gamma, and delta. We show an overall robust immune response, regardless of variant identity, leading to reduction in viral load in target organs, prevention of morbidity and mortality, as well as prevention of severe brain immune response, which follows infection with various variants.

Hfq-licensed RNA-RNA interactome in reveals a keystone sRNA.

The RNA chaperone Hfq plays important regulatory roles in many bacteria by facilitating the base pairing between small RNAs (sRNAs) and their cognate mRNA targets. In the gram-negative opportunistic pathogen , over a hundred putative sRNAs have been identified but for most, their regulatory targets remained unknown. Using RIL-seq with Hfq in , we identified the mRNA targets for dozens of previously known and unknown sRNAs.

Antiviral activity of glucosylceramide synthase inhibitors in alphavirus infection of the central nervous system.

Virus-induced CNS diseases impose a considerable human health burden worldwide. For many viral CNS infections, neither antiviral drugs nor vaccines are available. In this study, we examined whether the synthesis of glycosphingolipids, major membrane lipid constituents, could be used to establish an antiviral therapeutic target.

Initiation of fibronectin fibrillogenesis is an enzyme-dependent process.

Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here, we identify a nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl oxidase enzyme family members.