bluuebunny/crossref_metadata_2025_split huggingface dataset:
Instanton theory for Fermi’s golden rule and beyond
Authors: Ansari Imaad M. , Heller Eric R. , Trenins George , Richardson Jeremy O. 
Published: March 2022

Instanton theory provides a semiclassical approximation for computing quantum tunnelling effects in complex molecular systems. It is typically applied to proton-transfer reactions for which the Born–Oppenheimer approximation is valid. However, many processes in physics, chemistry and biology, such as electron transfers, are non-adiabatic and are correctly described instead using Fermi’s golden rule. In this work, we discuss how instanton theory can be generalized to treat these reactions in the golden-rule limit. We then extend the theory to treat fourth-order processes such as bridge-mediated electron transfer and apply the method to simulate an electron moving through a model system of three coupled quantum dots. By comparison with benchmark quantum calculations, we demonstrate that the instanton results are much more reliable than alternative approximations based on superexchange-mediated effective coupling or a classical sequential mechanism.
This article is part of the theme issue ‘Chemistry without the Born–Oppenheimer approximation’.
Tract-specific white matter microstructure alterations among young adultAPOEε4 carriers: A replication and extension study
Authors: Lissaman Rikki , Lancaster Thomas M. , Parker Greg D. , Graham Kim S. , Lawrence Andrew D. , Hodgetts Carl J. 
Published: March 2022

AbstractThe parahippocampal cingulum bundle (PHCB) connects regions known to be vulnerable to early Alzheimer’s disease (AD) pathology, such as posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at-risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E (APOE) ε4 allele – the strongest common genetic risk factor for AD – showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and connectivity have a significant role in posteromedial cortex vulnerability to amyloid-β and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.’s finding in a larger sample (N= 128; 40APOEε4 carriers, 88APOEε4 non-carriers) of young adults (age range: 19-33). Extending this work further, we also conducted exploratory analyses using a more advanced measure of microstructure: hindrance modulated orientational anisotropy (HMOA). These analyses included an investigation of hemispheric asymmetry in PHCB and ILF HMOA. Contrary to the original study, we observed no difference in PHCB microstructure betweenAPOEε4 carriers and non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings.APOEε4-related differences in ILF HMOA asymmetry were evident, however, with carriers demonstrating lower leftward asymmetry. Our findings indicate that young adultAPOEε4 carriers do not show alterations in PHCB microstructure, as observed by Hodgetts et al., but may show altered asymmetry in ILF microstructure.
The Envelope Protein of SARS-CoV-2 Inhibits Viral Protein Synthesis and Infectivity of Human Immunodeficiency Virus type 1 (HIV-1)
Authors: Henke Wyatt , Waisner Hope , Arachchige Sachith Polpitiya , Kalamvoki Maria , Stephens Edward 
Published: March 2022

ABSTRACTThe human coronavirus SARS-CoV-2 encodes for a small 75 amino acid transmembrane protein known as the envelope (E) protein. The E protein forms an ion channel, like the viroporins from human immunodeficiency virus type 1 (HIV-1) (Vpu) and influenza A virus (M2). Here, we analyzed HIV-1 virus infectivity in the presence of four different β-coronavirus E proteins. We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. This was also reflected in the levels of HIV-1 protein synthesis in cells. Mechanistically, we show that that the E protein neither affected reverse transcription nor genome integration. However, SARS-CoV-2 E protein activated the ER-stress pathway associated with the phosphorylation of eIF-2α, which is known to attenuate protein synthesis in cells. Finally, we show that these four E proteins and the SARS-CoV-2 N protein did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2) while the spike (S) proteins of SARS-CoV and SARS-CoV-2, and HIV-1 Vpu efficiently down-regulated cell surface BST-2 expression. The results of this study show for the first time that viroporins from a heterologous virus can suppress HIV-1 infection.IMPORTANCEThe E protein of coronaviruses is a viroporin that is required for efficient release of infectious virus and for viral pathogenicity. We determined if the E protein from four β-coronaviruses could restrict virus particle infectivity of HIV-1 infection. Our results indicate that the E proteins from SARS-CoV-2 and SARS-CoV potently restricted HIV-1 while those from MERS-CoV and HCoV-OC43 were less restrictive. Substitution of the highly conserved proline in the cytoplasmic domain of SARS-CoV-2 E abrogated the restriction on HIV-1 infection. Mechanistically, the SARS-CoV-2 E protein did not interfere with viral integration or RNA synthesis but rather reduced viral protein synthesis. We show that the E protein-initiated ER stress causing phosphorylation of eIF-2α, which is known to attenuate protein synthesis. Companion studies suggest that the E protein also triggers autophagy. These results show for the first time that a viroporin from a coronavirus can restrict infection of another virus.
Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation, France, December 2021 - February 2022
Authors: Bal Antonin , Simon Bruno , Destras Gregory , Chalvignac Richard , Semanas Quentin , Oblette Antoine , Queromes Gregory , Fanget Remi , Regue Hadrien , Morfin Florence , Valette Martine , Lina Bruno , Josset Laurence 
Published: March 2022

AbstractIn Dec 2021-Feb 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and we developed an unbiased bioinformatics method which can detect all co-infections irrespective of the SARS-CoV-2 lineages involved. Applied on 21,387 samples collected between weeks 49-2021 and 08-2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants.
Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function
Authors: Stolz Valentina , de Freitas e Silva Rafael , Rica Ramona , Zhu Ci , Preglej Teresa , Hamminger Patricia , Hainberger Daniela , Alteneder Marlis , Müller Lena , Waldherr Monika , Waltenberger Darina , Hladik Anastasiya , Agerer Benedikt , Schuster Michael , Frey Tobias , Krausgruber Thomas , Knapp Sylvia , Campbell Clarissa , Schmetterer Klaus , Trauner Michael , Bergthaler Andreas , Bock Christoph , Boucheron Nicole , Ellmeier Wilfried 
Published: March 2022

AbstractFOXP3+regulatory T cells (Treg cells) are key for immune homeostasis. Here, we reveal that nuclear receptor corepressor 1 (NCOR1) controls naïve and effector Treg cell states. Upon NCOR1 deletion in T cells, effector Treg cell frequencies were elevated in mice and inin vitro-generated human Treg cells. NCOR1-deficient Treg cells failed to protect mice from severe weight loss and intestinal inflammation associated with CD4+T cell transfer colitis, indicating impaired suppressive function. NCOR1 controls transcriptional integrity of Treg cells, since effector gene signatures were already upregulated in naïve NCOR1-deficient Treg cells while effector NCOR1-deficient Treg cells failed to repress genes associated with naïve Treg cells. Moreover, genes related to cholesterol homeostasis including targets of liver X receptor (LXR) were dysregulated in NCOR1-deficient Treg cells. However, genetic ablation of LXRβ in T cells did not revert the effects of NCOR1 deficiency, indicating that NCOR1 controls naïve and effector Treg cell subset composition independent from its ability to repress LXRβ-induced gene expression. Thus, our study reveals that NCOR1 maintains naïve and effector Treg cell states via regulating their transcriptional integrity. We also reveal a critical role for this epigenetic regulator in supporting the suppressive functions of Treg cellsin vivo.
Sudden unexpected death in epilepsy is prevented by blocking postictal hypoxia
Authors: George Antis G. , Farrell Jordan S. , Colangeli Roberto , Wall Alexandra K. , Gom Renaud C. , Kesler Mitchell T. , de la Hoz Cristiane L , Perera Tefani , Rho Jong M. , Kurrasch Deborah , Teskey G. Campbell 
Published: March 2022

AbstractEpilepsy is at times a fatal disease. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in people with intractable epilepsy and is defined by exclusion; non-accidental, non-toxicologic, and non-anatomic causes of death. While SUDEP often follows a bilateral tonic-clonic seizure, the mechanisms that ultimately lead to terminal apnea and then asystole remain elusive and there is a lack preventative treatments. Based on the observation that discrete seizures lead to local vasoconstriction, resulting in hypoperfusion, hypoxia and behavioural disturbances in the forebrain (Farrell et al., 2016), we reasoned that similar mechanisms may play a role in SUDEP when seizures invade the brainstem. Here we tested this neurovascular-based hypothesis of SUDEP in awake non-anesthetized mice by pharmacologically preventing seizure-induced vasoconstriction, with cyclooxygenase-2 or L-type calcium channel antagonists. In both acute and chronic mouse models of SUDEP, ibuprofen and nicardipine extended life. We also examined the potential role of spreading depolarization in the acute model of SUDEP. These data provide a proof of principle for the neurovascular hypothesis of SUDEP and the use of currently available treatments to prevent it.
The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction
Authors: Luqman-Fatah Ahmad , Watanabe Yuzo , Ishikawa Fuyuki , Moran John V. , Miyoshi Tomoichiro 
Published: March 2022

AbstractSome interferon stimulated genes (ISGs) encode proteins that inhibit LINE-1 (L1) retrotransposition. Here, we used immunoprecipitation followed by liquid chromatography-tandem mass spectrometry to identify proteins that associate with the L1 ORF1-encoded protein (ORF1p) in ribonucleoprotein particles. Three ISG proteins that interact with ORF1p inhibit retrotransposition: HECT and RLD domain containing E3 ubiquitin-protein ligase 5 (HERC5); 2’-5’-oligoadenylate synthetase-like (OASL); and helicase with zinc finger 2 (HELZ2). HERC5 destabilizes ORF1p, but does not affect its cellular localization. OASL impairs ORF1p cytoplasmic foci formation. HELZ2 recognizes sequences and/or structures within the L1 5’UTR to reduce L1 RNA, ORF1p, and ORF1p cytoplasmic foci levels. Overexpression of WT or reverse transcriptase-deficient L1s led to a modest induction of IFN-α expression, which was abrogated upon HELZ2 overexpression. Notably, IFN-α expression was enhanced upon overexpression of an ORF1p RNA binding mutant, suggesting ORF1p binding might protect L1 RNA from “triggering” IFN-α induction. Thus, ISG proteins can inhibit retrotransposition by different mechanisms.
The dynamics of adaptation to stress from standing genetic variation andde novomutations
Authors: Ament-Velásquez S. Lorena , Gilchrist Ciaran , Rêgo Alexandre , Bendixsen Devin P , Brice Claire , Grosse-Sommer Julie Michelle , Rafati Nima , Stelkens Rike 
Published: March 2022

AbstractAdaptation from standing genetic variation is an important process underlying evolution in natural populations but we rarely get the opportunity to observe the dynamics of fitness changes in real time. Here, we used the power of microbial experimental evolution and whole population sequencing to track the phenotypic and genomic changes of genetically diverse yeast populations in environments with different stress levels. We found that populations rapidly and in parallel increased in fitness in stressful environments. The founder’s genetic diversity was quickly depleted, however, not to the same degree in all populations and environments. Some populations fixed all ancestral variation in < 30 generations while others maintained diversity across hundreds of generations. We also observed parallelism at the gene and pathway level. Specifically, we detected up to seven genes harbouring multiple independent mutations in different populations, and a general enrichment for mutations affecting downstream effectors of the high-osmolarity-glycerol pathway in three out of four environments. Adaptation to the most stressful environment was characterised by the fast evolution of functional haploidy, likely driven by standing genetic variation. Almost 40% of all populations contained aneuploidies (losses or gains of chromosomes) at least once during experimental evolution. Some aneuploidies were maintained for hundreds of generations in parallel in different replicates, suggesting they were adaptive. This work shows that experimental evolution is a great tool to address the interplay between standing variation and the influx ofde novomutations, leading to a better understanding of the demographic and environmental drivers and constraints of a population’s capacity to adapt to environmental change.
S51 family peptidases provide resistance to peptidyl-nucleotide antibiotic McC
Authors: Yagmurov Eldar , Gilep Konstantin , Serebryakova Marina , Wolf Yuri I. , Dubiley Svetlana , Severinov Konstantin 
Published: March 2022

ABSTRACTMicrocin C-like compounds are natural Trojan horse peptide-nucleotide antibiotics produced by diverse bacteria. The ribosomally-synthesized peptide parts of these antibiotics are responsible for their facilitated transport into susceptible cells. Once inside the cell, the peptide part is degraded, releasing the toxic payload, an isoaspartyl-nucleotide that inhibits aspartyl-tRNA synthetase, an enzyme essential for protein synthesis. Bacteria that produce microcin C-like compounds have evolved multiple ways to avoid self-intoxication. Here, we describe a new strategy through the action of S51 family peptidases, which we name MccG. MccG cleaves the toxic isoaspartyl-nucleotide rendering it inactive. While some MccG homologs are encoded in gene clusters responsible for McC-like compounds biosynthesis, most are encoded by stand-alone genes whose products may provide basal level of resistance to peptide-nucleotide antibiotics in phylogenetically distant bacteria.SIGNIFICANCEWe identified a natural substrate for a major phylogenetic clade of poorly characterized S51 family proteases from bacteria. We show that these proteins can contribute to basal level of resistance to an important class of natural antibiotics.
Quantifying cerebral blood arrival times using hypoxia-mediated arterial BOLD contrast
Authors: Bhogal Alex A. , Sayin Ece Su , Poublanc Julien , Duffin Jim , Fisher Joseph A. , Sobcyzk Olivia , Mikulis David J. 
Published: March 2022

ABSTRACTCerebral blood arrival and tissue transit times are sensitive measures of the efficiency of tissue perfusion and can provide clinically meaningful information on collateral blood flow status. We exploit the arterial blood oxygen level dependent (BOLD) signal contrast established by precisely modulating arterial hemoglobin saturation using hypoxic respiratory challenges (dOHb-BOLD) to quantify arterial blood arrival times throughout the brain. A combination of hemodynamic lag with a modified carpet plot analysis yielded lag, onset (blood arrival), mean transit time (MTT) and hypoxic response information, which is indicative of relative total blood volume. Onset times averaged across 12 healthy subjects were 1.1 ± 0.4 and 1.9 ± 0.6 for cortical gray and deep white matter, respectively. The average whole brain MTT was 4.5 ± 0.9 seconds. The dOHb-BOLD response was 1.7 fold higher in grey versus white; in line with known differences in regional blood volume fraction. Our method was also applied in unilateral carotid artery occlusion patient, which revealed prolonged signal onset with normal perfusion in the affected hemisphere. In cases with exhausted reserve capacity or confounding flow effects such as vascular steal, dOHb-BOLD can potentially inform on collateral flow pathways to provide a valuable compliment to clinical vascular reactivity measures.
“Two-story building” of a ctenophore comb plate provides structural and functional integrity for motility of giant multicilia
Authors: Jokura Kei , Sato Yu , Shiba Kogiku , Inaba Kazuo 
Published: March 2022

SUMMARYComb plates (CPs) are large compound cilia uniquely seen in a basal metazoan group of ctenophores.1–3Tens of thousands of cilia are bundled in a CP via structures connecting adjacent cilia, called compartmenting lamella (CL), which are the basis for the structural iridescent color and the coordination of ciliary movement of the CP.4–6We previously reported the first component of CL, CTENO64, and found that it was convergently acquired in ctenophores and was essential for determination of ciliary orientation.3However, CTENO64 is localized only in the proximal region of the CL; therefore, the molecular architecture of CL over the entire length has not been elucidated. Here, we identified a second CL component, CTENO189. This ctenophore-specific protein was present in the distal region of the CL, with a localization clearly segregated from CTENO64. Knockdown of theCTENO189gene with morpholino antisense oligonucleotides resulted in complete loss of CLs in the distal region, but did not affect either the formation of CP or the orientation of each cilium. However, the hexagonal distribution of cilia was disarranged, and the metachronal coordination of CP along a comb row was lost in the CTENO189 morphants. The morphant CP showed asymmetric ciliary-type movement in normal seawater, and in a high-viscosity solution, it could not maintain the normal waveforms, becoming a symmetric flagellar-type. Our findings demonstrate a “two-story building” of CP, comprising the proximal CL, as the building foundation that rigidly fixes the ciliary orientation. The distal CL would reinforce the elastic connection among cilia to overcome the hydrodynamic drag of giant multiciliary plates.
Expression, purification and crystallization of a novel metagenome-derived salicylaldehyde dehydrogenase from Alpine soil
Authors: Dandare Shamsudeen Umar , Håkansson Maria , Svensson L. Anders , Timson David J. , Allen Christopher C. R. 
Published: March 2022

Salicylaldehyde dehydrogenase (SALD) catalyses the last reaction in the upper pathway of naphthalene degradation: the oxidation of salicylaldehyde to salicylate. This enzyme has been isolated and studied from a few organisms that belong to the betaproteobacteria and gammaproteobacteria, predominantly Pseudomonas putida. Furthermore, there is only one crystal structure of this enzyme, which was obtained from P. putida G7. Here, crystallographic studies and analysis of the crystal structure of an Alpine soil metagenome-derived SALD (SALDAP) from an alphaproteobacterium are presented. The SALDAP gene was discovered using gene-targeted sequence assembly and it was cloned into a pLATE51 vector. The recombinant protein was overexpressed in Escherichia coli BL21 (DE3) cells and the soluble protein was purified to homogeneity. The protein crystallized at 20°C and diffraction data from the crystals were collected at a resolution of 1.9 Å. The crystal belonged to the orthorhombic space group C2221, with unit-cell parameters a = 116.8, b = 121.7, c = 318.0 Å. Analysis of the crystal structure revealed its conformation to be similar to the organization of the aldehyde dehydrogenase superfamily with three domains: the catalytic, NAD+-binding and bridging domains. The crystal structure of NahF from P. putida G7 was found to be the best structural homologue of SALDAP, even though the enzymes share only 48% amino-acid identity. Interestingly, a carboxylic acid (protocatechuic acid) was found to be a putative ligand of the enzyme and differential scanning fluorimetry was employed to confirm ligand binding. These findings open up the possibility of studying the mechanism(s) of product inhibition and biocatalysis of carboxylic acids using this enzyme and other related aldehyde dehydrogenases.
Modelling and experimental verification of temperature effects on back electromotive force waveforms in a line start permanent magnet synchronous motor
Authors: Baranski Mariusz , Szelag Wojciech , Lyskawinski Wieslaw 
Published: March 2022

Purpose
This paper aims to elaborate the method and algorithm for the analysis of the influence of temperature on back electromotive force (BEMF) waveforms in a line start permanent magnet synchronous motor (LSPMSM).

Design/methodology/approach
The paper presents a finite element analysis of temperature influence on BEMF and back electromotive coefficient in a LSPMSM. In this paper, a two-dimensional field model of coupled electromagnetic and thermal phenomena in the LSPMSM was presented. The influence of temperature on magnetic properties of the permanent magnets as well as on electric and thermal properties of the materials has been taken into account. Simulation results have been compared to measurements. The selected results have been presented and discussed.

Findings
The simulations results are compared with measurements to confirm the adequacy of this approach to the analysis of coupled electromagnetic-thermal problems.

Originality/value
The paper offers appropriate author’s software for the transient and steady-state analysis of coupled electromagnetic and thermal problems in LSPMS motor.