Structural snapshots of phenuivirus cap-snatching and transcription.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes viral transcription by stealing host mRNA caps via a process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L protein in biologically relevant, transcription-specific states.

Policy makers believe money motivates more than it does.

To motivate contributions to public goods, should policy makers employ financial incentives like taxes, fines, subsidies, and rewards? While these are widely considered as the classic policy approach, a substantial academic literature suggests the impact of financial incentives is not always positive; they can sometimes fail or even backfire. To test whether policy makers are overly bullish about financial incentives, we asked county heads, mayors, and municipal government representatives of medium-to-large towns in Germany to predict the effects of a financial incentive on COVID-19 vaccination, and tested the exact same incentive in a field experiment involving all 41,548 inhabitants (clustered in 10,032 addresses) of the German town of Ravensburg. Whereas policy makers overwhelmingly predict that the financial incentive will increase vaccination-by 15.

Limited high-throughput screening compatibility of the phenuivirus cap-binding domain.

Bunyaviruses constitute a large and diverse group of viruses encompassing many emerging pathogens, such as Rift Valley fever virus (family Phenuiviridae), with public and veterinary health relevance but with very limited medical countermeasures are available. For the development of antiviral strategies, the identification and validation of virus-specific targets would be of high value. The cap-snatching mechanism is an essential process in the life cycle of bunyaviruses to produce capped mRNAs, which are then recognized and translated into viral proteins by the host cell translation machinery.

RNA to Rule Them All: Critical Steps in Lassa Virus Ribonucleoparticle Assembly and Recruitment.

Lassa virus is a negative-strand RNA virus with only four structural proteins that causes periodic outbreaks in West Africa. The nucleoprotein (NP) encapsidates the viral genome, forming ribonucleoprotein complexes (RNPs) together with the viral RNA and the L protein. RNPs must be continuously restructured during viral genome replication and transcription.

Structural and functional characterization of the Sin Nombre virus L protein.

The Bunyavirales order is a large and diverse group of segmented negative-strand RNA viruses. Several virus families within this order contain important human pathogens, including Sin Nombre virus (SNV) of the Hantaviridae. Despite the high epidemic potential of bunyaviruses, specific medical countermeasures such as vaccines or antivirals are missing.

The oxygen dissociation curve of blood in COVID-19-An update.

An impressive effect of the infection with SARS-Co-19 is the impairment of oxygen uptake due to lung injury. The reduced oxygen diffusion may potentially be counteracted by an increase in oxygen affinity of hemoglobin. However, hypoxia and anemia associated with COVID-19 usually decrease oxygen affinity due to a rise in [2,3-bisphosphoglycerate].

Liberté, Égalité, Crédibilité: An experimental study of citizens' perceptions of government responses to COVID-19 in eight countries.

During a global pandemic, individual views of government can be linked to citizens' trust and cooperation with government and their propensity to resist state policies or to take action that influences the course of a pandemic. This article explores citizens' assessments of government responses to COVID-19 as a function of policy substance (restrictions on civil liberties), information about performance, and socioeconomic inequity in outcomes. We conducted a survey experiment and analyzed data on over 7000 respondents from eight democratic countries.

Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.

Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity.

Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we present nine cryo-EM structures of the L protein in the apo-, promoter-bound pre-initiation and active RNA synthesis states.

Assessment of Right Ventricular Function With CT and Echocardiography in Patients With Severe Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

Objectives: Changes in right ventricular size and function are frequently observed in patients with severe acute respiratory distress syndrome. The majority of patients who receive venovenous extracorporeal membrane oxygenation undergo chest CT and transthoracic echocardiography. The aims of this study were to compare the use of CT and transthoracic echocardiography to evaluate the right ventricular function and to determine the prevalence of acute cor pulmonale in this patient population.

A case of broncho-cutaneous fistula secondary to tuberculosis successfully managed with awake veno-venous extracorporeal membrane oxygenation.

A broncho-cutaneous fistula (BCF) is a communicating tract between the bronchus and the cutaneous surface of the thoracic wall and can be the primary presenting sign of several disease processes. It has been associated with positive pressure ventilation (PPV), post pneumonectomy, thoracostomy tubes, perforating chest trauma, neoplasia and chronic empyema. We report a case of a 45-year-old immunocompetent man presenting with severe hypercapnic respiratory failure secondary to a BCF as a result of tuberculosis (TB)-related empyema necessitans.

A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID-19).

Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O ) affinity. Calculated oxygen tension at half-saturation (p ) was on average (±SD) 3·3 (3·13) mmHg lower than the normal p value (23·4 vs.

Structural and functional characterization of the severe fever with thrombocytopenia syndrome virus L protein.

The Bunyavirales order contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential.

Biochemical characterization of the Lassa virus L protein.

The L protein of arena- and bunyaviruses is structurally and functionally related to the orthomyxovirus polymerase complex. It plays a central role in the viral life cycle, as it replicates the virus genome and generates viral mRNA via a cap-snatching mechanism. Here, we aimed to biochemically characterize the L protein of Lassa virus, a human-pathogenic arenavirus endemic in West Africa.

Spatial characteristics of spontaneous and stimulus-induced individual functional connectivity networks in severe disorders of consciousness.

Background: Functional connectivity (fcMRI) analyses of resting state functional magnetic resonance imaging (fMRI) data revealed substantial differences between states of consciousness. The underlying cause-effect linkage, however, remains unknown to the present day. The aim of this study was to examine the relationship between fcMRI measures and Disorders of Consciousness (DOC) in resting state and under adequate stimulation.

Veno-arterio-venous ECMO for septic cardiomyopathy: a single-centre experience.

Introduction: The role of extracorporeal support for patients with septic shock remains unclear.

Methods: We conducted a retrospective analysis of our single-centre experience with veno-arterio-venous extracorporeal membrane oxygenation (VAV ECMO) in adult patients with severe respiratory failure and septic cardiomyopathy. Clinical data was extracted from electronic medical records including a dedicated ECMO referral and follow-up database.

Observation of Topological Bloch-State Defects and Their Merging Transition.

Topological defects in Bloch bands, such as Dirac points in graphene, and their resulting Berry phases play an important role for the electronic dynamics in solid state crystals. Such defects can arise in systems with a two-atomic basis due to the momentum-dependent coupling of the two sublattice states, which gives rise to a pseudospin texture. The topological defects appear as vortices in the azimuthal phase of this pseudospin texture.

Structural insights into reptarenavirus cap-snatching machinery.

Cap-snatching was first discovered in influenza virus. Structures of the involved domains of the influenza virus polymerase, namely the endonuclease in the PA subunit and the cap-binding domain in the PB2 subunit, have been solved. Cap-snatching endonucleases have also been demonstrated at the very N-terminus of the L proteins of mammarena-, orthobunya-, and hantaviruses.

Information processing in patients in vegetative and minimally conscious states.

Objective: Evaluation of a short two-tone oddball paradigm to discriminate between the vegetative state (VS) and minimal consciousness state (MCS) in a sample of patients with severe disorders of consciousness (DOC).

Method: EEG was recorded from 45 DOC patients and 14 healthy participants while listening to an auditory oddball paradigm presented in a passive - just listen - and an active - count the odd tones - condition. In patients, the experiment was repeated after a minimum of one week.

What kind of consciousness is minimal?

Primary Objective: A comparison between unitary and non-unitary views on minimal consciousness.

Research Design: First, unitary (all-or-none) and non-unitary (gradual or continuous) models of consciousness are defined as they have been developed in both philosophy and neurophysiology. Then, the implications of these ideas to the notion the minimally conscious state (MCS) are discussed.

Cyclolization of D-lysergic acid alkaloid peptides.

The tripeptide chains of the ergopeptines, a class of pharmacologically important D-lysergic acid alkaloid peptides, are arranged in a unique bicyclic cyclol based on an amino-terminal α-hydroxyamino acid and a terminal orthostructure. D-lysergyl-tripeptides are assembled by the nonribosomal peptide synthetases LPS1 and LPS2 of the ergot fungus Claviceps purpurea and released as N-(D-lysergyl-aminoacyl)-lactams. We show total enzymatic synthesis of ergopeptines catalyzed by a Fe²⁺/2-ketoglutarate-dependent dioxygenase (EasH) in conjunction with LPS1/LPS2.