bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases
Authors: Moraes Sofia N. , Becker Jordan T. , Moghadasi Seyed Arad , Shaban Nadine M. , Auerbach Ashley A. , Cheng Adam Z. , Harris Reuben S. 
Published: April 2022

AbstractViruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) of Epstein-Barr virus. Here, we investigate the mechanistic conservation and evolutionary origin of this innate immune counteraction strategy. First, we find that human gamma-herpesvirus RNRs engage A3B via largely distinct surfaces. Second, we show that RNR-mediated enzymatic inhibition and relocalization of A3B depend upon binding to different regions of the catalytic domain. Third, we show that the capability of viral RNRs to antagonize A3B is conserved among gamma-herpesviruses that infect humans and Old World monkeys that encode this enzyme but absent in homologous viruses that infect New World monkeys that naturally lack theA3Bgene. Finally, we reconstruct the ancestral primate A3B protein and demonstrate that it is active and similarly engaged by the RNRs from viruses that infect humans and Old World monkeys but not by the RNRs from viruses that infect New World monkeys. These results combine to indicate that the birth ofA3Bat a critical branchpoint in primate evolution may have been a driving force in selecting for an ancestral gamma-herpesvirus with an expanded RNR functionality through counteraction of this antiviral enzyme.
Delay-related activity in marmoset prefrontal cortex
Authors: Wong Raymond Ka , Selvanayagam Janahan , Johnston Kevin , Everling Stefan 
Published: April 2022

AbstractPersistent delay-period activity in prefrontal cortex (PFC) has long been regarded as a neural signature of working memory (WM). Electrophysiological investigations in macaque PFC have provided much insight into WM mechanisms, however a barrier to understanding is the fact that a portion of PFC lies buried within the principal sulcus in this species and is inaccessible for laminar electrophysiology or optical imaging. The relatively lissencephalic cortex of the New World common marmoset (Callithrix jacchus) circumvents such limitations. It remains unknown however, whether marmoset PFC neurons exhibit persistent activity. Here, we addressed this gap by conducting wireless electrophysiological recordings in PFC of marmosets performing a delayed-match-to-location task on a home cage-based touchscreen system. As in macaques, marmoset PFC neurons exhibited sample, delay, and response-related activity that was directionally tuned and linked to correct task performance. Models constructed from population activity consistently and accurately predicted stimulus location throughout the delay period, supporting a framework of delay activity in which mnemonic representations are relatively stable in time. Taken together, our findings support the existence of common neural mechanisms underlying WM performance in PFC of macaques and marmosets, and thus validate the marmoset as a suitable model animal for investigating the microcircuitry underlying WM.
Lumbar time-varying muscle synergies in trunk flexion and bending movements at different velocities
Authors: Rouchi Mahdi Bagheri , Davoudi Mehrdad , Meftahi Narges , Parnianpour Mohamad , Khalaf Kinda , Rashedi Ehsan 
Published: April 2022

AbstractPurposeAlthough the extent of which the central nervous system uses muscle synergies as a movement control strategy remains an open area of research, it is widely agreed that synergies facilitate the robustness of the neuromuscular system, allowing for effective postural control and flexible movement. This work aimed to investigate the muscle activation patterns of the trunk and time-varying muscle synergies using a novel 18-muscle 3-DOF, 3-D musculoskeletal model of the lumbar spine developed by the authors.Methods24 different biaxial trunk movements were simulated via the optimization of kinetic and kinematic measures towards obtaining the corresponding muscle activation patterns at 3 different velocities. These patterns were subsequently used to extract the principal (phasic and tonic) spatiotemporal synergies associated with the observed muscle activation patterns in the range of simulated movements.ResultsFour dominant synergies were able to explain a considerable percent (about 75%) of the variance of the simulated muscle activities. The extracted synergies were spatially tuned in the direction of the main simulated movements (flexion/extension and right/left lateral bending). The temporal patterns demonstrated gradual monotonic shifts in tonic synergies and biphasic modulatory components in phasic synergies with spatially tuned time-delays. The increase in velocity resulted in an elevated amplitude coefficient and accelerated activation of phasic synergies.ConclusionOur results suggest the plausibility of a time-varying synergies strategy in the dynamic control of trunk movement. Further work is needed to explore leveraging these concepts in various applications, such as rehabilitation and musculoskeletal biomechanics, towards providing more insight into the mechanisms underlying trunk stability and flexibility.
Nuclease proteins CifA and CifB promote spermatid DNA damage associated with symbiont-induced cytoplasmic incompatibility
Authors: Kaur Rupinder , Shropshire J. Dylan , Leigh Brittany A. , Bordenstein Seth R. 
Published: April 2022

SummaryThe worldwide endosymbiosis between arthropods and Wolbachia bacteria is an archetype for reproductive parasitism. This parasitic strategy rapidly increases the proportion of symbiont-transmitting mothers, and the most common form, cytoplasmic incompatibility (CI), impacts insect evolution and arboviral control strategies. During CI, sperms from symbiotic males kill embryos of aposymbiotic females via two nuclear-targeting proteins, CifA and CifB, that alter sperm chromatin organization in Drosophila melanogaster. Here we hypothesize that Cif proteins metabolize nucleic acids of developing sperm to initiate genome integrity changes. Using in vitro and in situ transgenic, mutant, enzymatic, and cytochemical assays, we show that CifA is a previously-unrecognized DNase and RNase, and CifB is a DNase. Notably, in vitro nuclease activity translates to in situ spermatid DNA damage at the canoe stage of spermiogenesis. Evolution-guided mutations ablate Cif enzymatic activity. Nucleic acid metabolism by Cif enzymes expands a fundamental understanding of the mechanism of symbiont-mediated reproductive parasitism.
ASTF1, an AP2/ERF-family transcription factor and ortholog of cultivated tomato LEAFLESS, is required for acylsugar biosynthesis
Authors: Mandal Sabyasachi , Rezenom Yohannes H. , McKnight Thomas D. 
Published: April 2022

ABSTRACTAcylsugars, specialized metabolites produced by solanaceous trichomes, provide protection against biotic and abiotic stresses. Here, we report ACYLSUGAR TRANSCRIPTION FACTOR1 (ASTF1/Sopen05g008450; AP2/ERF-family member) positively regulates acylsugar biosynthesis. Virus-induced gene silencing (VIGS) of ASTF1 in Solanum pennellii reduced acylsugar production by 65%. Most acylsugar (and several flavonoid) metabolic genes were downregulated in ASTF1-silenced plants, and these genes showed strong co-expression with ASTF1. In promoters of potential ASTF1-targets, we identified three enriched motifs, and one motif showed similarity with binding sites of other AP2/ERFs. Phylogenetic analysis and data mining indicated trichome-enriched expression of ASTF1 orthologs in several acylsugar-producing solanaceous species, suggesting a conserved role in acylsugar biosynthesis. This was supported by VIGS of ASTF1 orthologs in Nicotiana benthamiana. Broader phylogenetic analysis revealed relationships among specialized metabolic AP2/ERFs in several asterid species and provided clues about evolutionary emergence of acylsugar phenotype. Cultivated tomato ortholog (LEAFLESS/Solyc05g013540) has been reported to coordinate leaf initiation with transient expression at incipient primordia, and data mining revealed downregulation of trichome-preferentially-expressed genes, including acylsugar (and flavonoid) metabolic genes, in leafless mutants’ shoot apices, indicating remarkable spatiotemporal functional diversity. Our work will pave a way to disentangle acylsugar regulatory network and holds promise for future metabolic engineering of acylsugar production.
3’UTR-dependent dynamic changes in TP53 mRNA localization regulate p53 tumor suppressor activity
Authors: Hu Linshan , Misra Sweta , Karim Baktiar , Kuhn Skyler , Salotti Jacqueline , Basu Srikanta , Martin Nancy , Saylor Karen , Johnson Peter F. 
Published: April 2022

AbstractThe tumor suppressor p53 triggers senescence in response to oncogenic stress in primary cells. However, the mechanisms by which tumor cells retaining p53 bypass senescence are not fully understood. Here we report that p53 cytostatic activity is inhibited in tumor cells by the 3’ untranslated region (3’UTR) of its mRNA, without altering p53 levels. 3’UTR inhibition requires a long U-rich element (URE) and its binding protein, HuR. The 3’UTR excluded TP53 mRNAs from a perinuclear compartment containing the CK2 kinase, suppressing p53 phosphorylation on an activating CK2 site, Ser392. In primary cells undergoing oncogene-induced senescence and tumor cells treated with genotoxic agents, TP53 mRNAs became concentrated in the perinuclear cytoplasm, coinciding with p53 phosphorylation and activation by CK2. In both cases, perinuclear re-localization of TP53 transcripts required AMPKα2-dependent HuR nuclear translocation. ATM kinase activity was essential for DNA damage-induced spatial reprogramming of TP53 mRNAs, likely through phosphorylation and inactivation of MDM2. MDM2 was required for peripheral localization of TP53 transcripts and negatively regulated levels of the AMPKα2 activating kinase, CaMKKβ. Our findings reveal a critical role for 3’UTR sequences in suppressing p53 protein activity and provide a new mechanistic framework for p53 activation by DNA damaging agents.
Unbreakable DNA tension probes show that cell adhesion receptors detect the molecular force-extension curve of their ligands
Authors: Bender Rachel L. , Ogasawara Hiroaki , Kellner Anna V. , Velusamy Arventh , Salaita Khalid 
Published: April 2022

AbstractIntegrin receptors transduce the mechanical properties of the extracellular matrix. Past studies using DNA probes showed that integrins sense the magnitude of ligand forces with pN resolution. An open question is whether integrin receptors also sense the force-extension trajectory of their ligands. The challenge in addressing this question pertains to the lack of molecular probes that can control force-extension trajectories independently of force magnitude. To address this limitation, we synthesized two reversible DNA probes that fold with identical self-complementary domains but with different topologies. Thus, these probes unfold at the same steady-state force magnitude but following different kinetic pathways to reach the fully extended ssDNA state. Hairpin-like probes unzip with a low barrier of 14 pN while the pseudo-knot-like probes shear at 59 pN. Confirming that we had created probes with different barriers of unfolding, we quantified platelet integrin forces and measured 50-fold more tension signal with the unzipping probes over the shearing probes. In contrast, fibroblasts opened both probes to similar levels indicating more static forces. Surprisingly, fibroblast mechanotransduction markers, such as YAP levels, fibronectin production, actin organization, and integrin activation were significantly elevated on unzipping probes. This demonstrates that integrin receptors within focal adhesions sense the molecular force-extension profile of their ligands and not only the magnitude of equilibrium mechanical resistance.
A Python Package for the Localization of Protein Modifications in Mass Spectrometry Data
Authors: Barente Anthony S. , Villén Judit 
Published: April 2022

AbstractDetermining the correct localization of post-translational modifications (PTMs) on peptides aids in interpreting their effect on protein function. While most algorithms for this task are available as standalone applications or incorporated into software suites, improving their versatility through access from popular scripting languages facilitates experimentation and incorporation into novel workflows. Here we describe pyAscore, an efficient and versatile implementation of the Ascore algorithm in Python for scoring the localization of user defined PTMs in data dependent mass spectrometry. pyAscore can be used from the command line or imported into Python scripts and accepts standard file formats from popular software tools used in bottom-up proteomics. Access to internal objects for scoring and working with modified peptides adds to the toolbox for working with PTMs in Python. pyAscore and is available as an open source package for Python 3.6+ on all major operating systems and can be found at pyascore.readthedocs.io.
The heptaprenyl diphosphate synthase (Coq1) is the target of a lipophilic bisphosphonate that protects mice against Toxoplasma gondii infection
Authors: Sleda Melissa A. , Li Zhu-Hong , Behera Ranjan , Baierna Baihetiya , Li Catherine , Jumpathong Jomkwan , Malwal Satish R. , Kawamukai Makoto , Oldfield Eric , Moreno Silvia N. J. 
Published: April 2022

AbstractPrenyldiphosphate synthases catalyze the reaction of allylic diphosphates with one or more isopentenyl diphosphate molecules to form compounds such as farnesyl diphosphate, used in e.g. sterol biosynthesis and protein prenylation, as well as longer “polyprenyl” diphosphates, used in ubiquinone and menaquinone biosynthesis. Quinones play an essential role in electron transport and are associated with the inner mitochondrial membrane due to the presence of the polyprenyl group. In this work, we investigated the synthesis of the polyprenyl diphosphate that alkylates the ubiquinone ring precursor in Toxoplasma gondii, an opportunistic pathogen that causes serious disease in immunocompromised patients and the unborn fetus. The enzyme that catalyzes this early step of the ubiquinone synthesis is Coq1 (TgCoq1), and we show that it produces the C35 species, heptaprenyl diphosphate. TgCoq1 localizes to the mitochondrion, and is essential for in vitro T. gondii growth. We demonstrate that the growth defect of a T. gondii TgCoq1 mutant is rescued by complementation with a homologous TgCoq1 gene or with a (C45) solanesyl diphosphate synthase from Trypanosoma cruzi (TcSPPS). We find that a lipophilic bisphosphonate (BPH-1218) inhibits T. gondii growth at low nM concentrations, while overexpression of the TgCoq1 enzyme dramatically reduced growth inhibition by the bisphosphonate. Both the severe growth defect of the mutant and the inhibition by BPH-1218 were rescued by supplementation with a long chain (C30) ubiquinone (UQ6). Importantly, BPH-1218 also protected mice against a lethal T. gondii infection. TgCoq1 thus represents a potential drug target that could be exploited for improved chemotherapy of toxoplasmosis.ImportanceMillions of people are infected with Toxoplasma gondii and the available treatment for toxoplasmosis is not ideal. Most of the drugs currently used are only effective for the acute infection and treatment can trigger serious side-effects requiring changes in the therapeutic approach. There is, therefore, a compelling need for safe and effective treatments for toxoplasmosis. In this work, we characterize an enzyme of the mitochondrion of T. gondii that can be inhibited by an isoprenoid pathway inhibitor. We present evidence that demonstrate that inhibition of the enzyme is linked to parasite death. In addition, the drug is able to protect mice against a lethal dose of T. gondii. Our results thus reveal a promising chemotherapeutic target for the development of new medicines for toxoplasmosis.
Comprehensive Structural Variant Detection: From Mosaic to Population-Level
Authors: Smolka Moritz , Paulin Luis F. , Grochowski Christopher M. , Horner Dominic W. , Mahmoud Medhat , Behera Sairam , Kalef-Ezra Ester , Gandhi Mira , Hong Karl , Pehlivan Davut , Scholz Sonja W. , Carvalho Claudia M.B. , Proukakis Christos , Sedlazeck Fritz J 
Published: April 2022

AbstractLong-read Structural Variation (SV) calling remains a challenging but highly accurate way to identify complex genomic alterations. Here, we present Sniffles2, which is faster and more accurate than state-of-the-art SV caller across different coverages, sequencing technologies, and SV types. Furthermore, Sniffles2 solves the problem of family- to population-level SV calling to produce fully genotyped VCF files by introducing a gVCF file concept. Across 11 probands, we accurately identified causative SVs aroundMECP2, including highly complex alleles with three overlapping SVs. Sniffles2 also enables the detection of mosaic SVs in bulk long-read data. As a result, we successfully identified multiple mosaic SVs across a multiple system atrophy patient brain. The identified SV showed a remarkable diversity within the cingulate cortex, impacting both genes involved in neuron function and repetitive elements. In summary, we demonstrate the utility and versatility of Sniffles2 to identify SVs from the mosaic to population levels.
In Utero Activation of NK Cells in Congenital CMV Infection
Authors: Vaaben Anna V , Levan Justine , Nguyen Catherine B T , Callaway Perri C , Prahl Mary , Warrier Lakshmi , Nankya Felistas , Musinguzi Kenneth , Kakuru Abel , Muhindo Mary K , Dorsey Grant , Kamya Moses R. , Feeney Margaret E. 
Published: April 2022

AbstractBackgroundCongenital cytomegalovirus (CMV) infection is the most common infectious cause of birth defects and neurological damage in newborns. Despite a well-established role for NK cells in control of CMV infection in older children and adults, it remains unknown whether fetal NK cells can sense and respond to CMV infection acquired in utero.MethodsHere, we investigate the impact of congenital CMV infection on the neonatal NK cell repertoire by assessing the frequency, phenotype, and functional profile of NK cells in cord blood samples from newborns with congenital CMV and from uninfected controls enrolled in a birth cohort of Ugandan mothers and infants.ResultsWe find that neonatal NK cells from congenitally CMV infected newborns show increased expression of cytotoxic mediators, signs of maturation and activation, and an expansion of mature CD56-negative NK cells, an NK cell subset associated with chronic viral infections in adults. Activation was particularly prominent in NK cell subsets expressing the Fcγ receptor CD16, indicating a role for antibody-mediated immunity against CMV in utero.ConclusionThese findings demonstrate that NK cells can be activated in utero and suggest that NK cells may be an important component of the fetal and infant immune response against CMV.
Crystal structure of bis(ammonium) bis[pentaaqua(dimethylformamide)zinc(II)] decavanadate tetrahydrate
Authors: Ebrahimi Arash , Gyepes Róbert , Bujdoš Marek , Krivosudský Lukáš 
Published: April 2022

The crystalline product (NH4)2[Zn(C3H7NO)(H2O)5]2[V10O28]·4H2O was successfully isolated from an H2O/DMF solvent combination by evaporation at ambient temperature. The salt crystallizes in the P21/n space group. Imidazole, initially used in the synthesis but not present in the product, and DMF solvent appear to affect the synthesis and crystallization as structural-directing agents. In the title compound, the complex cation [Zn(H2O)5(DMF)]2+ acts as a counter-ion without being directly coordinated to the decavanadate anion. An extensive framework of hydrogen bonds integrates the whole architecture as evidenced by X-ray crystallography. The polyoxometalate [V10O28]6– lies on a center of symmetry while the complex cation [Zn(H2O)5(DMF)]2+ links three adjacent anions through a set of 2 + 2 + 3 hydrogen bonds.
A novel industrial AGV control strategy based on dual-wheel chassis model
Authors: Ding Hua , Huang Yanhong , Shi Jianqi , Shi Qi , Yang Yang 
Published: April 2022

Purpose
Automatic guided vehicles (AGVs) are widely used in industrial fields. But most control strategies merely take the lateral force into consideration. This will reduce the accuracy, stability and robustness and will pay additional costs. Therefore, this paper aims to design a control strategy that initially considers lateral force. Thereby, it will improve the accuracy, stability and robustness and reduce the overall cost of AGV.

Design/methodology/approach
To achieve the goal of comprehensively improving AGV operating performance, this paper presents a new scheme, combining the dual-wheeled chassis model (DCM) using proportional–integral–differential (PID) control and a supporting quick response (QR) code navigation technology. DCM is the core, which analyzes the deviation caused by lateral force. Then, DCM with PID control by the control law is combined to suppress the errors. Meanwhile, QR code navigation technology provides effective data support for the control strategy.

Findings
Most AGV experiments are carried out in a standard environment. However, this study prepares unfavorable scenarios and operating conditions for the experiments that generate detailed data to demonstrate this study’s strategy, which can make an accurate, stable and robust operation process of AGV under various adverse environmental and mechanical factors.

Originality/value
This study proposed DCM, fully considering lateral force and converting the force into velocity. Subsequently, PID controls the speed of two wheels to reduce the error. QR code provides an efficient and low – cost way to obtain information. The three are cleverly combined as a novel industrial AGV control strategy, which can comprehensively improve the operating performance while reducing overall costs.
The values in action character strengths model in addiction recovery: a case study
Authors: Ogilvie Lisa 
Published: April 2022

Purpose
The purpose of this study is to demonstrate how the values in action (VIA) character strengths model can be applied as a resource to support people in addiction recovery. The purpose of this is to appreciate the positive outcomes seen in other areas of research, applied to addiction recovery. To achieve this, a character strengths intervention has been designed and delivered as a case study. The objective of the intervention is to identify some of the strengths described by an individual in their account of recovery, ascertain their signature strengths through validated assessment and, based on the exploration of this information, support the individual in a reflective exercise to consider how their character strengths have positively affected their recovery to date and the effect this new knowledge could have on their ongoing recovery.

Design/methodology/approach
The VIA character strengths model has identified 24 positive qualities that are present in the human condition. In this case study, the VIA model is used to identify strengths from a first-hand account of the recovery process; the VIA character strengths survey is used to ascertain the signature strengths of the participant who is also the author of the account. Information from the strengths identification and VIA survey is explored, and a follow-up e-interview is conducted using questions designed to encourage the participant to reflect on the use of strengths in their present and ongoing recovery.

Findings
This case study shows that the VIA model of character strengths can be applied in addiction recovery to help people appreciate how they have used their character strengths in the recovery process, what their signature strengths are and how they can be used with good effect to improve their well-being and future recovery.

Originality/value
In this work, a new broad-spectrum approach using the VIA model of character strengths has been proposed to help people in addiction recovery use their own resources to improve their function, well-being and thus recovery.