bluuebunny/crossref_metadata_2025_split huggingface dataset:
A plant virus causes symptoms through the deployment of a host-mimicking protein domain to attract the insect vector
Authors: Gao Man , Aguilar Emmanuel , Garnelo Gómez Borja , Medina-Puche Laura , Fan Pengfei , Ontiveros Irene , Pan Shaojun , Tan Huang , von Roepenack-Lahaye Edda , Chen Na , Wang Xiao-Wei , Baulcombe David C , Bejarano Eduardo R , Díaz-Pendón Juan Antonio , Furutani Masahiko , Morita Miyo Terao , Lozano-Durán Rosa 
Published: December 2022

SUMMARYViruses are obligate intracellular parasites with limited proteomes that heavily rely on the cell molecular machinery for their multiplication and spread. Plant viruses frequently cause symptoms through interference with host developmental programs. Despite the agricultural relevance of symptom development in virus-infected crops, the molecular mechanisms underlying these viral effects remain elusive. Here, we show that the symptoms triggered by tomato yellow leaf curl virus (TYLCV) depend on the physical interaction between the host-mimicking domain of a virus-encoded protein, C4, and a plant-specific family of RCC1-like domain-containing (RLD) proteins. C4 outcompetes endogenous interactors of RLDs, disrupting RLD function in the regulation of endomembrane trafficking and polar auxin transport, ultimately leading to the developmental alterations recognized as symptoms of the viral infection. Importantly, symptoms do not have a detectable effect on the performance of the virus in the plant host, but they serve as attractants for the viral insect vector, the whiteflyBemisia tabaci, hence promoting pathogen spread. Our work uncovers the molecular underpinnings of the viral manipulation that leads to symptom development in the TYLCV-tomato pathosystem, and suggests that symptoms have evolved as a strategy to promote viral transmission by the insect vector. Given that most plant viruses are insect-transmitted, the principles described here might have broad applicability to crop-virus interactions.
Reductive Enzyme Cascades for Valorization of PET Deconstruction Products
Authors: Gopal Madan R. , Dickey Roman M. , Butler Neil D. , Talley Michael R. , Mohapatra Ashlesha , Watson Mary P. , Chen Wilfred , Kunjapur Aditya M. 
Published: December 2022

AbstractTo better incentivize the collection of plastic wastes, new chemical transformations must be developed that add value to plastic deconstruction products. Polyethylene terephthalate (PET) is a common plastic whose deconstruction through chemical or biological means has received much attention. However, a limited number of alternative products have been formed from PET deconstruction, and only a small share could serve as building blocks for alternative materials or therapeutics. Here, we demonstrate the production of useful mono-amine and diamine building blocks from known PET deconstruction products. We achieve this by designing one-pot biocatalytic transformations that are informed by the substrate specificity of an ω-transaminase and diverse carboxylic acid reductases (CAR) towards PET deconstruction products. We first establish that an ω-transaminase fromChromobacterium violaceum(cvTA) can efficiently catalyze amine transfer to potential PET-derived aldehydes to form the mono-aminepara-(aminomethyl)benzoic acid (pAMBA) or the diaminepara-xylylenediamine (pXYL). We then identified CAR orthologs that could perform the bifunctional reduction of TPA to terephthalaldehyde (TPAL) or the reduction ofmono-(2-hydroxyethyl) terephthalic acid (MHET) to its corresponding aldehyde. After characterizing 17 CARsin vitro, we show that the CAR fromSegniliparus rotundus(srCAR) had the highest observed activity on TPA. Given these newly elucidated substrate specificity results, we designed modular enzyme cascades based on coupling srCAR and cvTA in one-pot with enzymatic co-factor regeneration. When we supply TPA, we achieve a 69 ± 1% yield of pXYL, which is useful as a building block for materials. When we instead supply MHET and subsequently perform base-catalyzed ester hydrolysis, we achieve 70 ± 8% yield of pAMBA, which is useful for therapeutic applications and as a pharmaceutical building block. This work expands the breadth of products derived from PET deconstruction and lays the groundwork for eventual valorization of waste PET to higher-value chemicals and materials.GRAPHICAL ABSTRACT
RNA binding protein PRRC2B mediates translation of specific mRNAs and regulates cell cycle progression
Authors: Jiang Feng , Hedaya Omar M. , Khor EngSoon , Wu Jiangbin , Auguste Matthew , Yao Peng 
Published: December 2022

AbstractAccumulating evidence suggests that posttranscriptional control of gene expression, including RNA splicing, transport, modification, translation, and degradation, primarily relies on RNA binding proteins (RBPs). However, the functions of many RBPs remain understudied. Here, we characterized the function of a novel RBP, Proline-Rich Coiled-coil 2B (PRRC2B). Through photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation and sequencing (PAR-CLIP-seq), we identified transcriptome-wide CU- or GA-rich PRRC2B binding sites near the translation initiation codon on a specific cohort of mRNAs in HEK293T cells. These mRNAs, including oncogenes and cell cycle regulators such asCCND2(cyclin D2), exhibited decreased translation upon PRRC2B knockdown as revealed by polysome-associated RNA-seq, resulting in reduced G1/S phase transition and cell proliferation. Antisense oligonucleotides blocking PRRC2B interactions withCCND2mRNA decreased its translation, thus inhibiting G1/S transition and cell proliferation. Mechanistically, PRRC2B interactome analysis revealed RNA-independent interactions with eukaryotic translation initiation factors 3 (eIF3) and 4G2 (eIF4G2). The interaction with translation initiation factors is essential for PRRC2B function since the eIF3/eIF4G2-interacting defective mutant, unlike wild-type PRRC2B, failed to rescue the translation deficiency or cell proliferation inhibition caused by PRRC2B knockdown. Altogether, our findings reveal that PRRC2B is essential for efficiently translating specific proteins required for cell cycle progression and cell proliferation.Graphic Abstract
Heightened efficacy of anidulafungin when used in combination with manogepix or 5-flucytosine againstCandida auris in vitro
Authors: John Larissa L.H. , Thomson Darren D. , Bicanic Tihana , Hoenigl Martin , Brown Alistair J.P. , Harrison Thomas S. , Bignell Elaine 
Published: December 2022

AbstractCandida aurisis an emerging, multi-drug resistant fungal pathogen that causes refractory colonisation and life-threatening invasive nosocomial infections. The high proportion ofC. aurisisolates that display antifungal resistance severely limits treatment options. Combination therapies provide a possible strategy to enhance antifungal efficacy and prevent the emergence of further resistance. Therefore, we examined drug combinations using antifungals that are already in clinical use or undergoing clinical trials. Using checkerboard assays we screened combinations of 5-flucytosine and manogepix (the active form of the novel antifungal drug fosmanogepix) with anidulafungin, amphotericin B or voriconazole against drug resistant and susceptibleC. aurisisolates from clades I and III. Fractional inhibitory concentration indices (FICI values) of 0.28-0.75 and 0.36-1.02 were observed for combinations of anidulafungin with manogepix or 5-flucytosine, respectively, indicating synergistic activity. The high potency of these anidulafungin combinations was confirmed using live-cell microfluidics-assisted imaging of fungal growth. In summary, combinations of anidulafungin with manogepix or 5-flucytosine show great potential against both resistant and susceptibleC. aurisisolates.
Joint association of daytime sleep behaviors and dietary quality with the risk of dementia: A large prospective cohort study
Authors: Cao Xingqi , Zhang Jingyun , Li Xin , Yang Zhenqing , Sun Kaili , Chen Weiran , Zhu Yubo , Xu Qinglin , Xu Jiahui , He Liu , Li Xueqin , Tan Xiao , Zhang Lisan , Liu Zuyun 
Published: December 2022

AbstractBackgroundIdentifying modifiable risk factors of dementia is crucial for its early prevention. Daytime sleep behaviors (DSB) and diet are synergetic factors, both potentially important in maintaining cognitive health. However, whether they may jointly influence the risk of dementia in the general population remains unclear.MethodsThis study included 187,078 participants from the UK Biobank. DSB burden (low, medium, and high) was assessed through two questions regarding daytime sleepiness and napping. The Recommended Food Score (RFS) was calculated to assess dietary quality (by tertile). We ascertained incident dementia through linkage to hospital inpatient records. We used Cox proportional hazards regression models to estimate the associations.ResultsDuring a median follow-up of 10 years, we documented 1,351 cases with incident dementia. Compared with participants with low DSB burden, those with high DSB burden had a 21% (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.06, 1.38) higher risk of incident dementia. Dietary quality was negatively associated with dementia risk (HR for tertile 1 versus tertile 3: 1.42; 95% CI: 1.24, 1.63). There was a significant interaction between DSB burden and RFS (P for interaction = 0.027). Compared with participants with low DSB burden & high RFS, those with high DSB burden had higher risks of incident dementia, regardless of RFS level.ConclusionsHigh DSB burden and low dietary quality separately or in joint were significantly associated with higher risks of incident dementia, while high DSB burden seems to play a decisive role. Our findings imply that programs targeting the two behavioral factors, particularly the DSB, may help to prevent dementia.
Effectiveness of the Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine
Authors: Shrestha Nabin K. , Burke Patrick C. , Nowacki Amy S. , Simon James F. , Hagen Amanda , Gordon Steven M. 
Published: December 2022

ABSTRACTBackgroundThe purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19.MethodsEmployees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available, were included. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses.ResultsAmong 51017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent vaccinated state was associated with lower risk of COVID-19 during the BA.4/5 dominant (HR, .71; 95% C.I., .63-.79) and the BQ dominant (HR, .80; 95% C.I., .69-.94) phases, but decreased risk was not found during the XBB dominant phase (HR, .96; 95% C.I., .82-.1.12). Estimated vaccine effectiveness (VE) was 29% (95% C.I., 21%-37%), 20% (95% C.I., 6%-31%), and 4% (95% C.I., -12%-18%), during the BA.4/5, BQ, and XBB dominant phases, respectively. Risk of COVID-19 also increased with time since most recent prior COVID-19 episode and with the number of vaccine doses previously received.ConclusionsThe bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.SummaryAmong 51017 working-aged Cleveland Clinic employees, the bivalent COVID-19 vaccine was 29% effective in preventing infection while the BA.4/5 lineages were dominant, and 20% effective while the BQ lineages were. Effectiveness was not demonstrated when the XBB lineages were dominant.
Motor Skill Retention Impairments in Parkinson’s Disease: A Systematic Review with Meta-analysis
Authors: Cristini Jacopo , Parwanta Zohra , De las Heras Bernat , Medina-Rincon Almudena , Paquette Caroline , Doyon Julien , Dagher Alain , Steib Simon , Roig Marc 
Published: December 2022

AbstractThe ability to acquire and retain motor skills is essential for persons with Parkinson’s Disease (PD), who usually experience a progressive loss of mobility during the disease. Deficits in the rate of motor skill acquisition have been previously reported in these patients. Whether motor skill retention is also impaired is currently not known. We conducted a review that included 46 studies to determine whether, compared with neurologically intact individuals, motor skill retention is impaired in PD. Meta-analyses revealed that, following a single practice session, persons with PD have deficits in skill retention (SMD = −0.17; 95% CI = −0.32, −0.02;p= 0.0225). However, these deficits are task-specific, affecting sensory motor (SMD = −0.31; 95% CI −0.47, −0.15;p= 0.0002) and visuomotor adaptation (SMD = − 1.55; 95% CI = −2.32, −0.79;p= 0.0001) tasks, but not sequential fine motor (SMD = 0.17; 95% CI = −0.05, 0.39;p= 0.1292) and gross motor tasks (SMD = 0.04; 95% CI = −0.25, 0.33;p= 0.7771). Importantly, retention deficits became non-significant when augmented feedback during practice was provided. Similarly, additional sessions of motor practice restored the deficits observed in sensory motor tasks. Meta-regression analyses confirmed that retention deficits were independent of performance during motor skill acquisition, as well as the duration and severity of the disease. These results are in line with prominent neurodegenerative models of PD progression and emphasize the importance of developing targeted interventions to enhance motor memory processes supporting the retention of motor skills in people with PD.
Quantifying the rebound of influenza epidemics after relaxing nonpharmaceutical interventions during the coronavirus disease 2019 pandemic in China
Authors: Lei Hao , Yang Lei , Yang Mengya , Tang Jing , Yang Jiaying , Tan Minju , Yang Shigui , Wang Dayan , Shu Yuelong 
Published: December 2022

AbstractThe co-existence of coronavirus disease 2019 (COVID-19) and seasonal influenza epidemics has become a potential threat to human health, particularly in China in the oncoming season. However, with the relaxation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic, the rebound extent of the influenza activities is still poorly understood. In this study, we constructed a susceptible-vaccinated-infectious-recovered-susceptible (SVIRS) model to simulate influenza transmission and calibrated it using influenza surveillance data from 2018 to 2022. We projected the influenza transmission over the next 3 years using the SVIRS model. We observed that, in epidemiological year 2021–2022, the reproduction numbers of influenza in southern and northern China were reduced by 64.0% and 34.5%, respectively, compared with those before the pandemic. The percentage of people susceptible to influenza virus increased by 138.6% and 57.3% in southern and northern China by October 1, 2022, respectively. After relaxing NPIs, the potential accumulation of susceptibility to influenza infection may lead to a large-scale influenza outbreak in the year 2022-2023, the scale of which may be affected by the intensity of the NPIs. And later relaxation of NPIs in the year 2023 would not lead to much larger rebound of influenza activities in the year 2023-2024. To control the influenza epidemic to the pre-pandemic level after relaxing NPIs, the influenza vaccination rates in southern and northern China should increase to 53.8% and 33.8%, respectively. Vaccination for influenza should be advocated to reduce the potential reemergence of the influenza epidemic in the next few years.
Poly(2-oxazoline)-based polyplexes as a PEG-free plasmid DNA delivery platform
Authors: Yamaleyeva Dina N. , Makita Naoki , Hwang Duhyeong , Haney Matthew J. , Jordan Rainer , Kabanov Alexander V. 
Published: December 2022

AbstractThe present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a PEG-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying non-ionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, we employed azide-alkyne cycloaddition click chemistry methods. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, non-targeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either of these copolymers is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to non-mannosylated polyplexes. Thus, PEG-free, non-targeted DET- and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial non-lipid transfection reagent.
Passive identification of subjective preferences towards individual items using eye-tracking in a virtual reality environment
Authors: Gabay Michal , Schonberg Tom 
Published: December 2022

AbstractUsage of Virtual reality (VR) has been growing in many fields of research and therapy thanks to its immersive and gamified nature. Detection of the subjective experience of the users is thus essential for effective personalization of content. Eye-tracking (ET) data and specifically gaze, in two-dimensional tasks has been linked to value-based choices and emotional states. Therefore, here we aimed to develop a method for passive identification of subjective preferences based on ET data collected during a VR experience. For this purpose, we developed a naturalistic dynamic VR task where participants searched and looked at complex objects of pets and control shapes that appeared in pre-defined locations in random order. At the end of the task, participants ranked their preference, valence, and arousal of the items they saw during the task. ET data was recorded using a built-in binocular eye-tracker within the VR headset. We found that the median distance of gaze from the center of objects and the median gaze scan speed showed a significant interaction with object type (pets/shapes), as well as a significant positive relation to preference and valence rankings of pets. Our results suggest that ET could be used as a passive biomarker for detecting individual preferences and pleasantness, and in the future may enable successful personalization of VR content in real time for various applications.
A complex tissue-specific interplay between the Arabidopsis transcription factors AtMYB68, AtHB23, and AtPHL1 modulates primary and lateral root development and adaptation to salinity
Authors: Spies Fiorella Paola , Perotti María Florencia , Cho Yuhan , Jo Chang Ig , Hong Jong Chan , Chan Raquel Lía 
Published: December 2022

SUMMARYAdaptation to soil is a well-regulated process vital for plant life. AtHB23 is a homeodomain-leucine zipper I transcription factor (TF), previously revealed as crucial for plant survival in front of salinity conditions. We wondered whether this TF has partners to achieve this essential function.A TF cDNA library screening, Y2H, BiFC, and CoIP assays were complemented with expression analyses and phenotypic characterizations of silenced, mutant, overexpressor, and crossed plants in normal and salinity conditions.We revealed that AtHB23, AtPHL1, and AtMYB68 interact with each other, modulating root development and salinity response. The encoding genes coexpress in specific root tissues and developmental stages. In normal conditions,amiR68silenced plants have less initiated roots, the opposite phenotype to that showed byamiR23ones. AtMYB68 and AtPHL1 play contrary roles in lateral root elongation. Under salinity, where AtHB23 plays a crucial positive function, AtMYB68 cooperates with it, whereas AtPHL1 obstructs its action impacting survival ability and supporting the complex interaction between AtHB23, AtPHL1, and AtMYB68 in the primary and lateral roots. The root adaptation capability was associated with the amyloplast state.We identified new molecular players that through a complex relationship determine Arabidopsis root architecture and survival ability in salinity conditions.
Activation of β2-adrenergic receptors in microglia alleviates neuropathic hypersensitivity in mice
Authors: Damo Elisa , Agarwal Amit , Simonetti Manuela 
Published: December 2022

AbstractDrugs enhancing the availability of noradrenaline are gaining prominence in the therapy of chronic neuropathic pain. However, underlying mechanisms are not well understood, and research has thus far focused on α2-adrenergic receptors and neuronal excitability. Adrenergic receptors are also expressed on glial cells, but their roles toward antinociception are not well deciphered. This study addresses the contribution of β2-adrenergic receptors (β2-ARs) to the therapeutic modulation of neuropathic pain in mice. We report that selective activation of β2-ARs with Formoterol inhibits pro-inflammatory signaling in microgliaex-vivoand nerve injury-induced structural remodeling and functional activation of microgliain vivo. Systemic delivery of Formoterol inhibits behaviors related to neuropathic pain, such as mechanical hypersensitivity, cold allodynia and the aversive component of pain, and reverses chronically established neuropathic pain. Using conditional gene targeting for microglia-specific deletion of β2-ARs, we demonstrate that the anti-allodynic effects of Formoterol are primarily mediated by microglia. Although Formoterol also reduces astrogliosis at late stages of neuropathic pain, these functions are unrelated to β2-AR signaling in microglia. Our results underline the value of developing microglial β2-AR agonists for relief from neuropathic pain and clarify mechanistic underpinnings.Graphical Abstract