RNA language models predict mutations that improve RNA function.

Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. RNA structure prediction is not yet possible due to a lack of high-quality reference data associated with organismal phenotypes that could inform RNA function. We present GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB).

The Structure and Function of the Bacterial Osmotically Inducible Protein Y.

The ability to adapt to osmotically diverse and fluctuating environments is critical to the survival and resilience of bacteria that colonize the human gut and urinary tract. Environmental stress often provides cross-protection against other challenges and increases antibiotic tolerance of bacteria. Thus, it is critical to understand how E.

Scalable noninvasive amplicon-based precision sequencing (SNAPseq) for genetic diagnosis and screening of β-thalassemia and sickle cell disease using a next-generation sequencing platform.

β-hemoglobinopathies such as β-thalassemia (BT) and Sickle cell disease (SCD) are inherited monogenic blood disorders with significant global burden. Hence, early and affordable diagnosis can alleviate morbidity and reduce mortality given the lack of effective cure. Currently, Sanger sequencing is considered to be the gold standard genetic test for BT and SCD, but it has a very low throughput requiring multiple amplicons and more sequencing reactions to cover the entire HBB gene.

Single-protein Diffusion in the Periplasm of Escherichia coli.

The width of the periplasmic space of Gram-negative bacteria is only about 25-30 nm along the long axis of the cell, which affects free diffusion of (macro)molecules. We have performed single-particle displacement measurements and diffusion simulation studies to determine the impact of confinement on the apparent mobility of proteins in the periplasm of Escherichia coli. The diffusion of a reporter protein and of OsmY, an osmotically regulated periplasmic protein, is characterized by a fast and slow component regardless of the osmotic conditions.

Insights Into Clinical Outcomes of Acute Pancreatitis With Concomitant Acute Myocardial Infarction Using the National Inpatient Sample Database.

Acute pancreatitis (AP) and acute coronary syndrome (ACS) are common conditions, occasionally sharing overlapping symptoms, posing various clinical challenges. This study aims to investigate the demographics, outcomes, and risk factors of patients admitted with AP and ACS using the National Inpatient Sample database. The database from 2016 to 2019 was analyzed, identifying patients with a primary diagnosis of AP and dividing them into 2 groups: those with ACS and those without (non-ACS).

Super-resolving microscopy reveals the localizations and movement dynamics of stressosome proteins in Listeria monocytogenes.

The human pathogen Listeria monocytogenes can cope with severe environmental challenges, for which the high molecular weight stressosome complex acts as the sensing hub in a complicated signal transduction pathway. Here, we show the dynamics and functional roles of the stressosome protein RsbR1 and its paralogue, the blue-light receptor RsbL, using photo-activated localization microscopy combined with single-particle tracking and single-molecule displacement mapping and supported by physiological studies. In live cells, RsbR1 is present in multiple states: in protomers with RsbS, large clusters of stressosome complexes, and in connection with the plasma membrane via Prli42.

Deployment of iron uptake machineries as targets against drug resistant strains of mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB) requires a perpetual supply of iron for its sustenance. Iron scarcity and its limited availability in the host environment because of an encounter of various sites during the establishment of infection has led to the evolution of strategies for iron uptake, which includes biosynthesis of iron-chelating molecules called siderophores, Heme uptake pathways, recently discovered host iron transport protein receptors like glyceraldehyde-3-phosphate dehydrogenase and the development of machinery for proper storage of the acquired iron and its regulation. The components of the iron uptake machineries are viable targets in multidrug-resistant tuberculosis, some of which include the MmpL3 heme transfer protein, MbtA enzyme, and the ESX-3 system, while employment of approaches like the synthesis of siderophore drug conjugates, heme analogs, xenosiderophores as drug delivery agents, and the blockade of siderophore recycling are encouraged too.

How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids?

N-α-acetylation is a frequently occurring post-translational modification in eukaryotic proteins. It has manifold physiological consequences on the regulation and function of several proteins, with emerging studies suggesting that it is a global regulator of stress responses. For decades, biochemical investigations into the precise role of the intrinsically disordered protein alpha-synuclein (αS) in the etiology of Parkinson's disease (PD) were performed using non-acetylated αS.

Association between inpatient palliative care encounter and 30-day all-cause readmissions after index hospitalization for chronic obstructive pulmonary disease.

Background: Studies exist on the association between inpatient Palliative Care Encounter (iPCE) and 30-day rehospitalization among cancer and several non-cancer conditions but limited in persons with Chronic Obstructive Pulmonary Disease (COPD).

Objective: To assess the association between an iPCE with the risk of 30-day rehospitalization after an index hospitalization for COPD.

Methods: We conducted a cross-sectional analysis of the Nationwide Readmissions Database (2010-2014).

Prognostic Model of COVID-19 Severity and Survival among Hospitalized Patients Using Machine Learning Techniques.

We conducted a statistical study and developed a machine learning model to triage COVID-19 patients affected during the height of the COVID-19 pandemic in Hong Kong based on their medical records and test results (features) collected during their hospitalization. The correlation between the values of these features is studied against discharge status and disease severity as a preliminary step to identify those features with a more pronounced effect on the patient outcome. Once identified, they constitute the inputs of four machine learning models, Decision Tree, Random Forest, Gradient and RUSBoosting, which predict both the Mortality and Severity associated with the disease.

Amphibian behavioral diversity offers insights into evolutionary neurobiology.

Recent studies have served to emphasize the unique placement of amphibians, composed of more than 8000 species, in the evolution of the brain. We provide an overview of the three amphibian orders and their respective ecologies, behaviors, and brain anatomy. Studies have probed the origins of independently evolved parental care strategies in frogs and the biophysical principles driving species-specific differences in courtship vocalization patterns.

Usage of Direct Acting Oral Anticoagulants in Cirrhotic and Non-Cirrhotic Portal Vein Thrombosis: A Systematic Review.

Thrombosis of the portal vein (PVT) is generally seen in the setting of liver cirrhosis and to a lesser extent in the absence of cirrhosis. There is no clear guidance in relation to approaching treatment with anticoagulation in this condition. The professional societies and guidelines recommend treatment with traditional anticoagulation like low-molecular-weight heparin and vitamin-K antagonists in patients presenting with acute portal vein thrombosis.

Chemogenetic Tags with Probe Exchange for Live-Cell Fluorescence Microscopy.

Fluorogenic protein tagging systems have been less developed for prokaryotes than for eukaryotic cell systems. Here, we extend the concept of noncovalent fluorogenic protein tags in bacteria by introducing transcription factor-based tags, namely, LmrR and RamR, for probe binding and fluorescence readout under aerobic and anaerobic conditions. We developed two chemogenetic protein tags that impart fluorogenicity and a longer fluorescence lifetime to reversibly bound organic fluorophores, hence the name Chemogenetic Tags with Probe Exchange (CTPEs).

Measurement of Protein Mobility in Reveals a Unique Tolerance to Osmotic Stress and Temperature Dependence of Diffusion.

Protein mobility in the cytoplasm is essential for cellular functions, and slow diffusion may limit the rates of biochemical reactions in the living cell. Here, we determined the apparent lateral diffusion coefficient ( ) of GFP in as a function of osmotic stress, temperature, and media composition. We find that is much less affected by hyperosmotic stress in than under similar conditions in and .

Case Report: Multiple Strokes and Digital Ischemia in a Young COVID-19 Patient.

COVID-19 is an infectious disease caused by SARS-CoV-2. This enveloped RNA coronavirus primarily has tropism for the respiratory tract. However, it has also been shown to have various extrapulmonary manifestations such as pulmonary embolism, ischemic strokes, deep venous thrombosis, or arterial thrombosis.

Functional Outcomes After Revascularization Procedures in Patients With Hemorrhagic Moyamoya Disease.

Background: Poor natural history of hemorrhagic Moyamoya disease (MMD) is related to high rehemorrhage rates between 32% and 61%. Postrevascularization, rehemorrhage rates reportedly decrease to 12% to 17%.

Objective: To evaluate long-term functional outcomes and rehemorrhage rates of hemorrhagic MMD patients treated with surgical revascularization and examine these in relation to clinical and radiological factors.

Long-term follow up data on difficult to treat intracranial arteriovenous malformations treated with the CyberKnife.

Introduction: The CyberKnife, a frameless, robotic, stereotactic device, has been developed to radiosurgically treat arteriovenous malformations (AVMs). While most AVMs are obliterated within two-to-three years, a subset remain recalcitrant; long-term data on these difficult to treat AVMs are limited in the neurosurgical literature.

Materials And Methods: A retrospective analysis of all patients who underwent CyberKnife treatment for intracranial AVMs at a single U.

Disruptive membrane interactions of alpha-synuclein aggregates.

Alpha synuclein (αS) is a ~14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on αS yet its physiological function remains largely elusive. The conversion of monomeric αS into oligomers and amyloid fibrils is believed to play a central role of the pathology of Parkinson's disease (PD).

Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients.

Objective: The authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).

Methods: The authors retrospectively assessed treatment outcomes 5-18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22-83 years).

Intracranial Hemorrhage in Deep Vein Thrombosis/Pulmonary Embolus Patients Without Atrial Fibrillation.

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE.

Using time-varying models to estimate post-transplant survival in pediatric liver transplant recipients.

Purpose: To distinguish clinical factors that have time-varying (as opposed to constant) impact upon patient and graft survival among pediatric liver transplant recipients.

Methods: Using national data from 2002 through 2013, we examined potential clinical and demographic covariates using Gray's piecewise constant time-varying coefficients (TVC) models. For both patient and graft survival, we estimated univariable and multivariable Gray's TVC, retaining significant covariates based on backward selection.