bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of heme homeostasis in
Staphylococcus aureus
through post-translational regulation of glutamyl-tRNA reductase
Authors: Leasure Catherine S. , Grunenwald Caroline M. , Choby Jacob E. , Sauer John-Demian , Skaar Eric P. 
Published: September 2023

ABSTRACT

Staphylococcus aureus
is an important human pathogen responsible for a variety of infections including skin and soft tissue infections, endocarditis, and sepsis. The combination of increasing antibiotic resistance in this pathogen and the lack of an efficacious vaccine underscores the importance of understanding how
S. aureus
maintains metabolic homeostasis in a variety of environments, particularly during infection. Within the host,
S. aureus
must regulate cellular levels of the cofactor heme to support enzymatic activities without encountering heme toxicity.
G
lutamyl
tR
NA
r
eductase (GtrR), the enzyme catalyzing the first committed step in heme synthesis, is an important regulatory node of heme synthesis in Bacteria, Archaea, and Plantae. In many organisms, heme status negatively regulates the abundance of GtrR, controlling flux through the heme synthesis pathway. We identified two residues within GtrR, H32 and R214, that are important for GtrR-heme binding. However, in strains expressing either GtrR
H32A
or GtrR
R214A
, heme homeostasis was not perturbed, suggesting an alternative mechanism of heme synthesis regulation occurs in
S. aureus
. In this regard, we report that heme synthesis is regulated through phosphorylation and dephosphorylation of GtrR by the serine/threonine kinase Stk1 and the phosphatase Stp1, respectively. Taken together, these results suggest that the mechanisms governing staphylococcal heme synthesis integrate both the availability of heme and the growth status of the cell.

IMPORTANCE

Staphylococcus aureus
represents a significant threat to human health. Heme is an iron-containing enzymatic cofactor that can be toxic at elevated levels. During infection,
S. aureus
must control heme levels to replicate and survive within the hostile host environment. We identified residues within a heme biosynthetic enzyme that are critical for heme binding
in vitro;
however, abrogation of heme binding is not sufficient to perturb heme homeostasis within
S. aureus
. This marks a divergence from previously reported mechanisms of heme-dependent regulation of the highly conserved enzyme glutamyl tRNA reductase (GtrR). Additionally, we link cell growth arrest to the modulation of heme levels through the post-translational regulation of GtrR by the kinase Stk1 and the phosphatase Stp1.
Antimicrobial resistance profiles of
Streptococcus suis
isolated from pigs, wild boars, and humans in France between 1994 and 2020
Authors: Dechêne-Tempier Manon , Jouy Eric , Bayon-Auboyer Marie-Hélène , Bougeard Stéphanie , Chauvin Claire , Libante Virginie , Payot Sophie , Marois-Créhan Corinne 
Published: September 2023

ABSTRACT

Streptococcus suis,
an emerging zoonotic pathogen, causes invasive infections and substantial economic losses in the pig industry worldwide. Antimicrobial resistance against 22 antibiotics was studied for 200
S
.
suis
strains collected in different geographical regions of France. Most of the strains (86%) showed resistance to at least one antibiotic with a low rate of resistance to fluoroquinolones, penicillins, pleuromutilin, and diaminopyrimidine-sulfonamides, and a higher rate to macrolides-lincosamides and tetracycline. Multi-resistance patterns were observed in 138 strains; three of them being resistant to six antibiotic families. Statistical analyses highlighted a decrease in the resistance to trimethoprim-sulfamethoxazole, in our collection, between the two periods studied—before 2010 and after 2015—as well as an impact of the geographical origin with a higher rate of resistance to macrolides-lincosamides and penicillin in Brittany than in the other French regions. Furthermore, macrolides-lincosamides and tetracycline resistance patterns were more likely to be found in pig isolates than in human and wild boar isolates. A difference in resistance was also observed between serotypes. Most of the penicillin-resistant strains belong to serotypes 1, 5, 9, 11, 12, 15, 27, and 29. Finally, penicillin and pleuromutilin resistances were mostly found in “non-clinical” isolates. The empirical treatment of human and porcine infections due to
S. suis
in France can therefore still be carried out with beta-lactams. However, this study emphasizes the need to monitor antimicrobial resistance in this zoonotic pathogen.
Fungal organic acid uptake of mineral-derived K is dependent on distance from carbon hotspot
Authors: Bhattacharjee Arunima , Velickovic Dusan , Richardson Jocelyn A. , Couvillion Sneha P. , Vandergrift Gregory W. , Qafoku Odeta , Taylor Michael J. , Jansson Janet K. , Hofmockel Kirsten , Anderton Christopher R. 
Published: September 2023

ABSTRACT

Fungal mineral weathering regulates the bioavailability of inorganic nutrients from mineral surfaces to organic matter and increase the bioavailable fraction of nutrients. Such weathering strategies are classified as biomechanical or biochemical. In the case of fungal uptake of mineral nutrients through biochemical weathering, it is widely hypothesized that uptake of inorganic nutrients occurs through organic acid chelation, but such processes have not been directly visualized. This is in part due to challenges in probing the complex and heterogeneous soil environment. Here, using an epoxy-based, mineral-doped soil micromodel platform, which emulates soil mineralogy and porosity, we visualize the molecular mechanisms of mineral weathering. Mass spectrometry imaging revealed differences in the distribution of fungal exudates, citric acid, and tartaric acid on the soil micromodels in presence of minerals. Citric acid was detected closer to the nutrient-rich inoculation point, whereas tartaric acid was highly abundant away from inoculation point. This suggested that the organic acid exuded by the fungi depended on the proximity from the carbon-rich organic substrate at the point of inoculation. Using a combination of X-ray fluorescence and X-ray near edge structure analysis, we identified citric acid- and tartaric acid-bound K within fungal hyphae networks grown in the presence of minerals. Combined, our results provide direct evidence that fungi uptake and transport mineral derived nutrient organic acid chelation. The results of this study provided unprecedented visualization of fungal uptake and transport of K
+
, while resolving the indirect weathering mechanism of fungal K uptake from mineral interfaces.

IMPORTANCE
Fungal species are foundational members of soil ecosystems with vital contributions that support interspecies resource translocation. The minute details of these biogeochemical processes are poorly investigated. Here, we addressed this knowledge gap by probing fungal growth in a novel mineral-doped soil micromodel platform using spatially-resolved imaging methodologies. We found that fungi uptake K from K-rich minerals using organic acids exuded in a distance-dependent manner from a carbon-rich hotspot. While identification of specific mechanisms within soil remains challenging, our findings demonstrate the significance of reduced complexity platforms such as the mineral-doped micromodel in probing biogeochemical processes. These findings provide visualization into hyphal uptake and transport of mineral-derived nutrients in a resource-limited environment.
Interferon inhibits the release of herpes simplex virus-1 from the axons of sensory neurons
Authors: Danastas Kevin , Guo Gerry , Merjane Jessica , Hong Nathan , Larsen Ava , Miranda-Saksena Monica , Cunningham Anthony L. 
Published: September 2023

ABSTRACT
Herpes simplex virus-1 (HSV-1) has evolved mechanisms to evade the host immune system and limit the antiviral effects induced by interferon (IFN) produced by local epithelial and immune cells. In this study, we determined the effects of type I, II, and III IFNs on HSV-1 release from sensory axons. Using compartmentalized microfluidic devices separating axons from the neuronal cell bodies, we showed that treating axons with type I (IFNα and IFNβ), type II (IFNγ), and type III (IFNλ) IFNs inhibited the release of HSV-1 from axons, without altering the anterograde axonal transport of viral components. Furthermore, we showed that only type II IFN induced a cell-wide response following axonal treatment, with phosphorylated STAT1 and STAT3 present along axons and in the neuronal cell body, whereas type I and III IFNs only induced a local STAT1 and STAT3 response in axons. We also showed that HSV-1 infection alone, in the absence of exogenous IFN, activated STAT1 and STAT3 in both neuronal cell bodies and along axons. However, HSV-1 infection restricted the translocation of pSTAT1 and pSTAT3 to the nucleus even in the presence of IFNs, suggesting viral evasion mechanisms are involved in limiting the IFN response in the neuronal cell body. Overall, our study indicates a key and greater antiviral role of IFNs in inhibiting HSV-1 release from axon termini than in the ganglia during recurrent infections and identifies a novel intervention site, the neuro-epidermal junction, for the development of new immunotherapies.

IMPORTANCE
Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel back along sensory nerves, where it can form lesions in the oral and genital mucosa, eye, and skin, or be shed asymptomatically. New treatment options are needed as resistance is emerging to current antiviral therapies. Here, we show that interferons (IFNs) are capable of blocking virus release from nerve endings, potentially stopping HSV-1 transmission into the skin. Furthermore, we show that IFNγ has the potential to have widespread antiviral effects in the neuron and may have additional effects on HSV-1 reactivation. Together, this study identifies new targets for the development of immunotherapies to stop the spread of HSV-1 from the nerves into the skin.
Complete genome sequences of agricultural azole-resistant
Penicillium rubens
encoding CYP51A and ERG11 paralogues
Authors: Gauthier Jeff , Mohammadi Sima , Huffman Jesse , Lawal Opeyemi U. , Kukavica-Ibrulj Irena , Potvin Marianne , Goodridge Lawrence , Levesque Roger C. 
Published: September 2023

ABSTRACT

Azoles are major antifungals in agriculture and medicine. However, the surge of intrinsic azole resistance is critical for public health. Here, we present the complete long-read sequencing of three azole-resistant
Penicillium rubens
from food crops. The presence of CYP51A and ERG11 paralogues was confirmed, as in other azole-resistant
P. rubens
.
Assessment and verification of chemical inactivation of peste des petits ruminants virus by virus isolation following virus capture using Nanotrap magnetic virus particles
Authors: Das Amaresh , Ahmed Zaheer , Xu Lizhe , Jia Wei 
Published: September 2023

ABSTRACT
This study reports development and optimization of a new method for the assessment and verification of the inactivation of peste des petits ruminants virus (PPRV) by chemical agents, including Triton X-100 and commercially available viral lysis buffers. Virus inactivation was confirmed by virus isolation (VI) on Vero cells following capture of the potential residual viruses from treated samples using Nanotrap magnetic virus particles (NMVPs). Since chemical agents are cytotoxic, treated PPRV samples could not be used directly for VI on Vero cell monolayers; instead, they were diluted in Eagle’s Minimum Essential Medium (EMEM) to neutralize cytotoxicity and then subjected to virus capture using NMVPs. The NMVPs and the captured viruses were then clarified on a magnetic stand, reconstituted in EMEM, and inoculated onto Vero cells that were examined for cytopathic effect (CPE). No CPE was observed on cells inoculated with treated viruses captured by NMVPs; but CPE was observed on cells inoculated with untreated viruses, including those captured by NMVPs. For further verification, the supernatants of the VI cultures (treated or untreated) were subjected to RNA extraction and PPRV-specific real-time RT-PCR (RT-qPCR). The cycle threshold values were undetectable for the supernatants of VI cultures inoculated with NMVPs reconstituted from treated PPRV but detectable for the supernatants of VI cultures inoculated with untreated PPRV or the NMVPs reconstituted from untreated PPRV, indicating complete inactivation of PPRV. This new method of verification of virus inactivation using NMVPs can be applied to other high impact viruses of agricultural or public health importance.

IMPORTANCE
Research including diagnosis on highly contagious viruses at the molecular level such as PCR and next-generation sequencing requires complete inactivation of the virus to ensure biosafety and biosecurity so that any accidental release of the virus does not compromise the safety of the susceptible population and the environment. In this work, peste des petits ruminants virus (PPRV) was inactivated with chemical agents, and the virus inactivation was confirmed by virus isolation (VI) using Vero cells. Since the chemical agents are cytotoxic, inactivated virus (PPRV) was diluted 1:100 to neutralize cytotoxicity, and the residual viruses (if any) were captured using Nanotrap magnetic virus particles (NMVPs). The NMVPs and the captured viruses were subjected to VI. No CPE was observed, indicating complete inactivation, and the results were further supported by real-time RT-PCR. This new protocol to verify virus inactivation can be applicable to other viruses.
Lipid metabolic reprogramming of hepatic CD4
+
T cells during SIV infection
Authors: Clain Julien A. , Boutrais Steven , Dewatines Juliette , Racine Gina , Rabezanahary Henintsoa , Droit Arnaud , Zghidi-Abouzid Ouafa , Estaquier Jérôme 
Published: September 2023

ABSTRACT

While liver inflammation is associated with AIDS, little is known so far about hepatic CD4
+
T cells. By using the simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) model, we aimed to characterize CD4
+
T cells. The phenotype of CD4
+
T cells was assessed by flow cytometry from uninfected (
n
= 3) and infected RMs, with either SIVmac251 (
n
= 6) or SHIVSF162p3 (
n
= 6). After cell sorting of hepatic CD4
+
T cells, viral DNA quantification and RNA sequencing were performed.Thus, we demonstrated that liver CD4
+
T cells strongly expressed the SIV coreceptor, CCR5. We showed that viremia was negatively correlated with the percentage of hepatic effector memory CD4
+
T cells. Consistent with viral sensing, inflammatory and interferon gene transcripts were increased. We also highlighted the presence of harmful CD4
+
T cells expressing
GZMA
and members of
TGFB
that could contribute to fuel inflammation and fibrosis. Whereas RNA sequencing demonstrated activated CD4
+
T cells displaying higher levels of mitoribosome and membrane lipid synthesis transcripts, few genes were related to glycolysis and oxidative phosphorylation, which are essential to sustain activated T cells. Furthermore, we observed lower levels of mitochondrial DNA and higher levels of genes associated with damaged organelles (reticulophagy and mitophagy). Altogether, our data revealed that activated hepatic CD4
+
T cells are reprogrammed to lipid metabolism. Thus, strategies aiming to reprogram T cell metabolism with effector function could be of interest for controlling viral infection and preventing liver disorders.

IMPORTANCE

Human immunodeficiency virus (HIV) infection may cause liver diseases, associated with inflammation and tissue injury, contributing to comorbidity in people living with HIV. Paradoxically, the contribution of hepatic CD4
+
T cells remains largely underestimated. Herein, we used the model of simian immunodeficiency virus (SIV)-infected rhesus macaques to access liver tissue. Our work demonstrates that hepatic CD4
+
T cells express CCR5, the main viral coreceptor, and are infected. Viral infection is associated with the presence of inflamed and activated hepatic CD4
+
T cells expressing cytotoxic molecules. Furthermore, hepatic CD4
+
T cells are reprogrammed toward lipid metabolism after SIV infection. Altogether, our findings shed new light on hepatic CD4
+
T cell profile that could contribute to liver injury following viral infection.
Impact of storage time in dried blood samples (DBS) and dried plasma samples (DPS) for point-of-care hepatitis C virus (HCV) RNA quantification and HCV core antigen detection
Authors: Troyano-Hernáez Paloma , Herrador Pedro , Gea Francisco , Romero-Hernández Beatriz , Reina Gabriel , Albillos Agustín , Galán Juan Carlos , Holguín África 
Published: September 2023

ABSTRACT

The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log
10
IU/mL (DBS) and 0.3 log
10
IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values.

IMPORTANCE
Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.
Control optimization for parametric Hamiltonians by pulse reconstruction
Authors: Luchi Piero , Turro Francesco , Quaglioni Sofia , Wu Xian , Amitrano Valentina , Wendt Kyle , DuBois Jonathan L. , Pederiva Francesco 
Published: September 2023

AbstractOptimal control techniques provide a means to tailor the control pulses required to generate customized quantum gates, which helps to improve the resilience of quantum simulations to gate errors and device noise. However, the significant amount of (classical) computation required to generate customized gates can quickly undermine the effectiveness of this approach, especially when pulse optimization needs to be iterated. We propose a method to reduce the computational time required to generate the control pulse for a Hamiltonian that is parametrically dependent on a time-varying quantity. We use simple interpolation schemes to accurately reconstruct the control pulses from a set of pulses obtained in advance for a discrete set of predetermined parameter values. We obtain a reconstruction with very high fidelity and a significant reduction in computational effort. We report the results of the application of the proposed method to device-level quantum simulations of the unitary (real) time evolution of two interacting neutrons based on superconducting qubits.
A Flexible Multiband Dendritic Structure Fractal Antenna for 4G/5G/WLAN/Bluetooth Applications
Authors: Yu Zhen , Zhang Guodong , Ran Xiaoying , Niu Ruirong , Sun Runzhi , Lin Ziheng , Lu Zewei 
Published: September 2023

In this study, a flexible multiband fractal antenna mimicking dendrite structure is proposed and designed by combining bionics and fractal theory. The dendritic structure of neurons is extracted and simplified into a simple and clear geometric structure. The initial antenna model is obtained by fractal operation on the geometric structure, and finally, four effective bands are obtained. The antenna is printed on a

50

∗

70

∗

0.1

mm3 polyimide dielectric board and fed by a coplanar waveguide. This paper discusses the effect of the human body on the performance of the antenna and the robustness of the antenna in the bending regime. The gain, efficiency, and cross-polarization of the antenna were tested using a microwave anechoic chamber. The measured antenna covers 1.37 GHz-1.93 GHz (relative bandwidth 35%), 2.25 GHz-2.51 GHz (relative bandwidth 10.7%), 3.13 GHz-3.81 GHz (relative bandwidth 19.3%), and 4.46 GHz-5.5 GHz (relative bandwidth 21.1%) four operating frequency bands. The maximum gain is 6.05 dBi and the maximum efficiency is 91.05%. The antenna can be used for Bluetooth WLAN (Wireless Local Area Network), 4G (4th Generation Communication System), 5G (5th Generation Mobile Communication System), WiMAX (Worldwide Interoperability for Microwave Access), etc. The test results are in good agreement with the simulation results, which proves that the antenna can meet various wireless communication requirements.
Druggable Targets in Cytokine Release Syndromes
Authors: Luri-Rey Carlos , Eguren-Santamaria Iñaki , Matos Ignacio , Berraondo Pedro , Melero Ignacio 
Published: September 2023

Summary
Bispecific T-cell engagers and chimeric antigen receptor T cells share the problem of eliciting acute systemic inflammation episodes known as cytokine release syndrome. Knowledge on the sequential waves of cytokines that can be neutralized with clinically available agents is crucial to prevent or treat this condition without jeopardizing the antitumor therapeutic outcome.
See related article by Leclercq-Cohen et al., p. 4449
Utilização da distração óssea no tratamento de pacientes com Sequência de Pierre Robin
Authors: Santos Igor Bustamante Ferreira dos , Machado Ingrid Aquino , Barros Lorena de Oliveira , Souza Ana Cristina Rodrigues Antunes de 
Published: September 2023

Introdução: A sequência de Pierre Robin é uma tríade de anomalias caracterizada por micrognatia, glossoptose e fissura palatina. Estão descritas na literatura algumas modalidades de tratamento para melhorar a qualidade de vida dos pacientes com esta síndrome, como a distração óssea. Objetivo: Este artigo científico objetivou demonstrar a possibilidade de utilização da distração óssea na correção das anomalias advindas desta alteração. Materiais e métodos: Realizou-se uma busca de artigos em bases de dados eletrônicos e foram selecionados artigos escritos nos idiomas inglês e português, cujos temas abordados iam de encontro com o proposto por este trabalho e auxiliavam em sua produção. Resultados: Indivíduos com a Sequência de Pierre Robin apresentam características funcionais e estéticas comprometidas, afetando, consequentemente, as suas qualidades de vida. Conclusão: Concluiu-se que para uma reabilitação e um tratamento adequado, a técnica da distração óssea se mostrou muito eficaz. Cabe ressaltar a necessidade essencial de uma equipe multidisciplinar em atuação.