bluuebunny/crossref_metadata_2025_split huggingface dataset:
The plant stress hormone jasmonic acid evokes defensive responses in streptomycetes
Authors: van der Meij Anne , Elsayed Somayah S. , Du Chao , Willemse Joost , Wood Thomas M. , Martin Nathaniel I. , Raaijmakers Jos M. , van Wezel Gilles P. 
Published: October 2023

ABSTRACT

Actinobacteria are prevalent in the rhizosphere and phyllosphere of diverse plant species where they help to enhance tolerance of plants against biotic and abiotic stresses. Here, we show that the plant hormones jasmonic acid (JA) and methyl jasmonate (MeJA) affect the growth, development, and specialized metabolism of
Streptomyces
. Exposure of
Streptomyces coelicolor
to JA or MeJA led to enhanced production of the polyketide antibiotic actinorhodin. JA also exhibited toxicity toward
Streptomyces
and
Streptacidiphilus
at higher concentrations, whereby streptomycetes were more tolerant to JA than members of the genus
Streptacidiphilus
. Tolerance to JA could be linked to its conjugation by the bacteria with glutamine. Additionally, JA conjugates with valine, tyrosine, phenylalanine, and leucine/isoleucine were identified. In contrast to JA, synthetic JA conjugates failed to activate antibiotic production and showed significantly reduced toxicity. Thus, our findings provide insights into a previously unknown defense mechanism deployed by
Streptomycetaceae
to a plant hormone. The underlying mechanism encompasses the attachment of amino acids to JA, which in turn safeguards the bacteria against the harmful impacts of the plant hormone. This study adds to the growing body of evidence that plant hormones can have a significant impact on members of the plant microbiome by affecting their growth, development, and secondary metabolism.

IMPORTANCE

Microorganisms that live on or inside plants can influence plant growth and health. Among the plant-associated bacteria, streptomycetes play an important role in defense against plant diseases, but the underlying mechanisms are not well understood. Here, we demonstrate that the plant hormones jasmonic acid (JA) and methyl jasmonate directly affect the life cycle of streptomycetes by modulating antibiotic synthesis and promoting faster development. Moreover, the plant hormones specifically stimulate the synthesis of the polyketide antibiotic actinorhodin in
Streptomyces coelicolor
. JA is then modified in the cell by amino acid conjugation, thereby quenching toxicity. Collectively, these results provide new insight into the impact of a key plant hormone on diverse phenotypic responses of streptomycetes.
Multi-center clinical evaluation of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay in nasopharyngeal swab specimens from symptomatic individuals
Authors: Sasidharan Anjana , Selvarangan Rangaraj , Konrad Kennah , Faron Matthew L. , Shakir Salika M. , Hillyard David , McCall Robert K. , McHardy Ian H. , Goldberg David C. , Dunn James J. , Greninger Alexander L. , Lansang Christine , Bogh Rachel , Remillard Carmelle V. 
Published: October 2023

ABSTRACT
The symptomology is overlapping for respiratory infections due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), influenza A/B viruses, and respiratory syncytial virus (RSV). Accurate detection is essential for proper medical management decisions. This study evaluated the clinical performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay in nasopharyngeal swab (NPS) specimens from individuals of all ages with signs and symptoms of respiratory infection consistent with COVID-19, influenza, or RSV. Retrospective known-positive and prospectively obtained residual NPS specimens were collected during two respiratory seasons in the USA. Clinical performance was established by comparing Panther Fusion SARS-CoV-2/Flu assay results to a three-molecular assay composite comparator interpretation for SARS-CoV-2 and to the FDA-cleared Panther Fusion Flu A/B/RSV assay results for all non-SARS-CoV-2 targets. A total of 1,900 prospective and 95 retrospective NPS specimens were included in the analyses. The overall prevalence in prospectively obtained specimens was 20.7% for SARS-CoV-2, 6.7% for influenza A, and 0.7% for RSV; all influenza B-positive specimens were retrospective specimens. The positive percent agreement of the Panther Fusion assay was 96.9% (378/390) for SARS-CoV-2, 98.0% (121/123) for influenza A virus, 95.2% (20/21) for influenza B virus, and 96.6% (57/59) for RSV. The negative percent agreement was ≥98.5% for all target viruses. Specimens with discordant Panther Fusion SARS/Flu/RSV assay results all had cycle threshold values of ≥32.4 (by comparator or by Panther Fusion SARS/Flu/RSV assay). Only five co-infections were detected in the study specimens. The Panther Fusion SARS-CoV-2/Flu/RSV assay provides highly sensitive and specific detection of SARS-CoV-2, influenza A virus, influenza B virus, and RSV in NPS specimens.
Vaccine-induced antibody Fc-effector functions in humans immunized with a combination Ad26.RSV.preF/RSV preF protein vaccine
Authors: Bartsch Yannic C. , Cizmeci Deniz , Yuan Dansu , Mehta Nickita , Tolboom Jeroen , De Paepe Els , van Heesbeen Roy , Sadoff Jerald , Comeaux Christy A. , Heijnen Esther , Callendret Benoit , Alter Galit , Bastian Arangassery Rosemary 
Published: October 2023

ABSTRACT

An Ad26.RSV.preF/RSV preF protein combination vaccine demonstrated 80.0% vaccine efficacy for the prevention of respiratory syncytial virus (RSV)-mediated lower respiratory tract disease in a phase 2b study. In addition to neutralizing antibodies, Fc-effector functions are associated with protective immunity against RSV. Here, vaccine-induced Fc-effector functions were evaluated for the Ad26.RSV.preF/RSV preF protein vaccine in a subset of participants enrolled in a phase 1/2a study. RSV preF-specific antibody subclasses, isotypes, Fcγ receptor binding, and Fc-effector functions were evaluated on days 1 (pre-vaccination), 15, 29, and 183. Compared with Ad26.RSV.preF or RSV preF protein alone, the combination vaccine induced greater Fc-effector functions, including antibody-dependent neutrophil phagocytosis and antibody-dependent natural killer cell activation. Despite RSV pre-exposure, antibody-dependent neutrophil phagocytosis and antibody-dependent natural killer cell activation were not observed at baseline but were induced
de novo
following vaccination. Compared with the individual vaccine components, the combination vaccine induced a more polyfunctional antibody response.

IMPORTANCE
Respiratory syncytial virus (RSV) can cause serious illness in older adults (i.e., those aged ≥60 years). Because options for RSV prophylaxis and treatment are limited, the prevention of RSV-mediated illness in older adults remains an important unmet medical need. Data from prior studies suggest that Fc-effector functions are important for protection against RSV infection. In this work, we show that the investigational Ad26.RSV.preF/RSV preF protein vaccine induced Fc-effector functional immune responses in adults aged ≥60 years who were enrolled in a phase 1/2a regimen selection study of Ad26.RSV.preF/RSV preF protein. These results demonstrate the breadth of the immune responses induced by the Ad26.RSV.preF/RSV preF protein vaccine.
African swine fever virus B175L inhibits the type I interferon pathway by targeting STING and 2′3′-cGAMP
Authors: Ranathunga Lakmal , Dodantenna Niranjan , Cha Ji-Won , Chathuranga Kiramage , Chathuranga W. A. Gayan , Weerawardhana Asela , Subasinghe Ashan , Haluwana D. K. , Gamage Nuwan , Lee Jong-Soo 
Published: October 2023

ABSTRACT
Type I interferon (IFN)-mediated responses operate a pivotal role in the first line of host immune defense against viruses. Upon DNA virus infection, DNA sensing cyclic GMP-AMP synthase-STING signal pathway is a key event in the IFN-mediated antiviral response and also a target of viral immune evasion. African swine fever (ASF) is a highly contagious, cross-border viral disease that often confers fatalities in domestic and feral pigs of all ages. African swine fever virus (ASFV), a causative agent of ASF, is a nucleocytoplasmic large DNA virus that masks critical elements of host immune system by several encoded proteins. In this study, we report a novel immune evasion mechanism of ASFV B175L to block type I IFN signaling by targeting STING and 2'3'-cyclic GMP-AMP (2′3′-cGAMP). We found that ASFV B175L significantly inhibited the DNA virus-induced IFN-β production and IFN-mediated signaling responses. The conserved zf-FCS motif of ASFV B175L competitively interacted with both cGAMP and the cyclic dinucleotide binding domain of STING. Remarkably, the R238 and Y240 amino acids of STING were crucial for interaction with ASFV B175L. Consequently, this interaction inhibits the interaction between cGAMP and STING, thereby inhibiting downstream signaling including STING polymerization and phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3 for antiviral signaling. Taken together, these results highlight the critical role of ASFV B175L in suppression of IFN responses and provide a new target to guide live-attenuated ASFV vaccine.

IMPORTANCE
African swine fever virus (ASFV), the only known DNA arbovirus, is the causative agent of African swine fever (ASF), an acutely contagious disease in pigs. ASF has recently become a crisis in the pig industry in recent years, but there are no commercially available vaccines. Studying the immune evasion mechanisms of ASFV proteins is important for the understanding the pathogenesis of ASFV and essential information for the development of an effective live-attenuated ASFV vaccines. Here, we identified ASFV B175L, previously uncharacterized proteins that inhibit type I interferon signaling by targeting STING and 2′3′-cGAMP. The conserved B175L-zf-FCS motif specifically interacted with both cGAMP and the R238 and Y240 amino acids of STING. Consequently, this interaction interferes with the interaction of cGAMP and STING, thereby inhibiting downstream signaling of IFN-mediated antiviral responses. This novel mechanism of B175L opens a new avenue as one of the ASFV virulent genes that can contribute to the advancement of ASFV live-attenuated vaccines.
Alphavirus-induced transcriptional and translational shutoffs play major roles in blocking the formation of stress granules
Authors: Frolova Elena I. , Palchevska Oksana , Dominguez Francisco , Frolov Ilya 
Published: October 2023

ABSTRACT
Alphavirus infections cause multiple alterations in the intracellular environment that can have both positive and negative effects on viral replication. The Old World alphaviruses, such as Sindbis (SINV), chikungunya (CHIKV), and Semliki Forest viruses, hinder the ability of vertebrate cells to form stress granules (SGs). Previously, this inhibitory function was attributed to the hypervariable domain (HVD) of nsP3, which sequesters the key SG components, G3BP1 and G3BP2, and to the nsP3 macro domain. The macro domain possesses ADP-ribosylhydrolase activity, which can diminish the ADP-ribosylation of G3BP1 during viral replication. However, our recent findings do not support the prevailing notions. We demonstrate that the interactions between SINV- or CHIKV-specific nsP3s and G3BPs, and the ADP-ribosylhydrolase activity are not major contributors to the inhibitory process, at least when nsP3 is expressed at biologically relevant levels. Instead, the primary factors responsible for suppressing SG formation are virus-induced transcriptional and translational shutoffs that rapidly develop within the first few hours post infection. Poorly replicating SINV variants carrying mutated nsP3 HVD still inhibit SG development even in the presence of sodium arsenite (NaAs). Conversely, SINV mutants lacking transcription and/or translation inhibitory functions lose their ability to inhibit SG formation, despite expressing high levels of wt nsP3. Moreover, we found that stable cell lines expressing GFP-nsP3 fusions retain the capacity to form SGs when exposed to NaAs. However, our results do not rule out the possibility that additional alphavirus-induced changes in cell biology may contribute to the suppression of SG formation.

IMPORTANCE
Our study highlights the mechanisms behind the cell’s resistance to stress granule (SG) formation after infection with Old World alphaviruses. Shortly after infection, the replication of these viruses hinders the cell’s ability to form SGs, even when exposed to chemical inducers such as sodium arsenite. This resistance is primarily attributed to virus-induced transcriptional and translational shutoffs, rather than interactions between the viral nsP3 and the key components of SGs, G3BP1/2, or the ADP-ribosylhydrolase activity of nsP3 macro domain. While interactions between G3BPs and nsP3 are essential for the formation of viral replication complexes, their role in regulating SG development appears to be small, if any. Cells harboring replicating viruses or replicons with lower abilities to inhibit transcription and/or translation, but expressing wild-type nsP3, retain the ability for SG development. Understanding these mechanisms of regulation of SG formation contributes to our knowledge of viral replication and the intricate relationships between alphaviruses and host cells.
3′UTR of ALV-J can affect viral replication through promoting transcription and mRNA nuclear export
Authors: Xu Moru , Qian Kun , Shao Hongxia , Yao Yongxiu , Nair Venugopal , Ye Jianqiang , Qin Aijian 
Published: October 2023

ABSTRACT
3′ Untranslated regions (3′UTRs) play a crucial role in gene transcription and post-transcriptional regulation. During the past 30 years, subgroup J avian leukosis virus (ALV-J) had accumulated large-scale mutations in 3′UTRs of their proviral genome. In this study, we summarize five kinds of mutant 3′UTRs in ALV-J and analyzed their potential functions. Results indicated that ALV-J strains containing different 3′UTRs showed different replication ability, while this divergence is tissue preferential, especially in chicken embryonic liver cells and chicken endothelial cells. All 3′UTRs can assist intron-containing viral mRNA nuclear export, with no salient differences among the five forms. The half-life of ALV-J mRNA is not influenced by different 3′UTRs. However, 3′UTRs can drastically boost mRNA transcription in a cell-specific manner. These different 3′UTRs can promote foreign genes expression. Our results provide novel insight into the pathogenicity and life cycle of ALV-J.

IMPORTANCE
3′UTRs can affect gene transcription and post-transcriptional regulation in multiple ways, further influencing the function of proteins in a unique manner. Recently, ALV-J has been mutating and evolving rapidly, especially the 3′UTR of viral genome. Meanwhile, clinical symptoms caused by ALV-J have changed significantly. In this study, we found that the ALV-J strains containing △-r-TM-type 3′UTR are the most abundant. By constructing ALV-J infectious clones and subgenomic vectors containing different 3′UTRs, we prove that 3′UTRs directly affect viral tissue preference and can promote virus replication as an enhancer. ALV-J strain containing 3′UTR of △-r-TM proliferated fastest in primary cells. All five forms of 3′UTRs can assist intron-containing viral mRNA nuclear export, with similar efficiency. ALV-J mRNA half-life is not influenced by different 3′UTRs. Our results dissect the roles of 3′UTR on regulating viral replication and pathogenicity, providing novel insights into potential anti-viral strategies.
Real-life experience in two cases of secondary prophylaxis with letermovir for CMV infection in solid organ transplantation
Authors: Pérez Ana-Belén , Santos Bravo Marta , Vidal-Verdú Elisa , Páez-Vega Aurora , Vaquero-Barrios José-Manuel , Montero José-Luis , Marcos María-Ángeles , Torre-Cisneros Julián 
Published: October 2023

ABSTRACT

The use of valganciclovir as secondary prophylaxis for cytomegalovirus (CMV) infection in solid organ transplantation (SOT) is the most prevalent therapeutic choice, but it has been dismissed by the presence of resistance and toxicity. Letermovir (LMV) is indicated as primary prophylaxis in hematopoietic stem cell transplantation, but there is scarce clinical data on its use as secondary prophylaxis in SOT. We present two cases of SOT recipients (lung, liver) who underwent LMV secondary prophylaxis. One patient developed the L595S (
UL97
)-resistant mutation to ganciclovir/valganciclovir and experienced several CMV relapses under LMV therapy, but no LMV resistance mutations were detected. The second patient developed the C325F (
UL56
)-resistant mutation to LMV under secondary prophylaxis which was rescued by foscarnet. This observation reviews previously published clinical data on LMV secondary prophylaxis and recommends a cautious use of LMV in the clinical practice due to the early development of
UL56
resistance mutations.

IMPORTANCE
This observation provides comprehensive data on the clinical correlates of both cytomegalovirus (CMV) genotypic follow-up and clinical monitoring and outcomes for two different solid organ transplantation recipients that received letermovir as secondary prophylaxis. Our study emphasizes that monitoring of CMV disease in the patient and early genotypic detection of resistance mutations are essential when using new antiviral drugs for off-label indication in patients experiencing CMV relapses or not responding to standard antiviral therapy. These cases and the bibliography reviewed can be helpful for other researchers and clinicians working in the field to optimize the use of new treatments for transplant recipients since drug-resistant CMV infection is an important emerging problem even with new developments in antiviral treatment.
Effect of short-term, climate-driven sediment deposition on tectonically controlled alluvial channel incision
Authors: Wang Xueliang , Clague John J. , Frattini Paolo , Qi Shengwen , Lan Hengxing , Zhang Wen , Li Lihui , Sun Juanjuan , Crosta Giovanni Battista 
Published: October 2023

Abstract
Debate about relations between rates of fluvial incision and time (the “Sadler effect”) continues, impeding the use of incision rates to infer tectonic and climatic processes. There is a dearth of detailed field evidence that can be used to explore the coupling between tectonics and climate in controlling alluvial channel geometry and incision rates over time scales of 102–105 yr. We present field data from the Rumei watershed of southeast Tibet, which we obtained by mapping and dating late Pleistocene (ca. 135 ka) fluvial terraces and related channels, measuring channel hydraulic geometry, and calculating channel steepness indexes and incision rates. The evidence indicates that climate forcing is the main driver of sediment production and delivery to streams in the watershed. New aggradation events altered alluvial valley and channel geometry and, coupled with tectonic uplift, affected the rate of channel incision in the catchment. We propose a conceptual model that links uplift-driven incision (II) to channel aggradation induced by climate change, which is valid in catchments and other areas. We conclude that the reduction in incision depth caused by climate-driven channel aggradation is significant on short time scales (102–105 yr), and its cumulative effect contributes to the “Sadler effect” on long time scales (&gt;106 yr).
Specificities of the Fourier Transform Infrared Spectroscopic Methodology and Interpretation of Spectroscopic Data in Microbiological Analyses
Authors: Kamnev A. A. , Tugarova A. V. 
Published: October 2023

Abstract
In this mini-review, some of the most significant, from the authors’ point of view, features of the methodology of Fourier transform infrared (FTIR) spectroscopy and interpretation of experimentally obtained spectroscopic data are considered, as applied to the molecular spectrochemical analysis of microbiological objects using examples published in the specialised scientific literature mainly in recent years. Examples of typical inaccuracies and errors both of a methodological nature and arising in the interpretation of spectroscopic data are also presented and briefly discussed.
Effect of an electronic medical record nudge to improve quality improvement program tracking of neuraxial catheter replacements in obstetric patients
Authors: Fedoruk Kelly , Xie James , Wang Ellen , Fowler Cedar , Riley Edward , Carvalho Brendan 
Published: October 2023

BackgroundMonitoring complications associated with medical procedures requires reliable and accurate record keeping. Nudge reminders executed by way of electronic medical record (EMR) alerts influence clinician behaviour. We hypothesised that the introduction of an EMR nudge would improve documentation of replaced neuraxial blocks by obstetric anaesthesiologists at our institution.MethodsWe developed an EMR nudge that would alert the physician to a replaced neuraxial block if two or more neuraxial procedure notes in a single patient encounter were detected. The nudge encouraged physicians to document neuraxial block replacements in our institution’s quality improvement database. We assessed the rate of physician adherence to replaced neuraxial block charting prior to the introduction of the nudge (January 2019–September 2019) and after the implementation (October 2019–December 2020).Results494 encounters during the chart review period, January 2019–December 2020, required a neuraxial block replacement, representing an actual neuraxial replacement rate of 6.3% prior to the introduction of the nudge in October 2019. This rate was largely unchanged (6.2%) after the introduction of the nudge (0.1% difference, 95% CI: −0.0119 to 0.0099). Prior to the introduction of the nudge, the proportion of correctly charted failed/replaced blocks in our quality improvement database was 80.0%, and after nudge introduction, the rate was 96.2% (p value <0.00001, OR=6.32, 95% CI: 3.15 to 12.66). A p-chart of the monthly adherence rate demonstrated sustained improvement over time.ConclusionsEMR nudge technology significantly improved adherence with quality metric monitoring of neuraxial catheter replacement in obstetric patients. The results imply that data collection for quality metric databases of neuraxial block failures and replacements that rely on clinician memory without a nudge are likely under-reporting neuraxial block failures and replacements. This study supports widespread implementation of nudges in EMRs to improve quality metric reporting.