bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR–Cas9-mediated editing of starch branching enzymes results in altered starch structure in Brassica napus
Authors: Wang Liping , Wang You , Makhmoudova Amina , Nitschke Felix , Tetlow Ian J , Emes Michael J 
Published: November 2021

Abstract
Starch branching enzymes (SBEs) are one of the major classes of enzymes that catalyze starch biosynthesis in plants. Here, we utilized the clustered regularly interspaced short palindromic repeats–CRISPR associated protein 9 (CRISPR–Cas9)-mediated gene editing system to investigate the effects of SBE mutation on starch structure and turnover in the oilseed crop Brassica napus. Multiple single-guide RNA (sgRNA) expression cassettes were assembled into a binary vector and two rounds of transformation were employed to edit all six BnaSBE genes. All mutations were heterozygous monoallelic or biallelic, and no chimeric mutations were detected from a total of 216 editing events. Previously unannotated gene duplication events associated with two BnaSBE genes were characterized through analysis of DNA sequencing chromatograms, reflecting the complexity of genetic information in B. napus. Five Cas9-free homozygous mutant lines carrying two to six mutations of BnaSBE were obtained, allowing us to compare the effect of editing different BnaSBE isoforms. We also found that in the sextuple sbe mutant, although indels were introduced at the genomic DNA level, an alternate transcript of one BnaSBE2.1 gene bypassed the indel-induced frame shift and was translated to a modified full-length protein. Subsequent analyses showed that the sextuple mutant possesses much lower SBE enzyme activity and starch branching frequency, higher starch-bound phosphate content, and altered pattern of amylopectin chain length distribution relative to wild-type (WT) plants. In the sextuple mutant, irregular starch granules and a slower rate of starch degradation during darkness were observed in rosette leaves. At the pod-filling stage, the sextuple mutant was distinguishable from WT plants by its thick main stem. This work demonstrates the applicability of the CRISPR–Cas9 system for the study of multi-gene families and for investigation of gene-dosage effects in the oil crop B. napus. It also highlights the need for rigorous analysis of CRISPR–Cas9-mutated plants, particularly with higher levels of ploidy, to ensure detection of gene duplications.
pHBMT1, a BAHD-family monolignol acyltransferase, mediates lignin acylation in poplar
Authors: de Vries Lisanne , MacKay Heather A , Smith Rebecca A , Mottiar Yaseen , Karlen Steven D , Unda Faride , Muirragui Emilia , Bingman Craig , Vander Meulen Kirk , Beebe Emily T , Fox Brian G , Ralph John , Mansfield Shawn D 
Published: November 2021

Abstract
Poplar (Populus) lignin is naturally acylated with p-hydroxybenzoate ester moieties. However, the enzyme(s) involved in the biosynthesis of the monolignol–p-hydroxybenzoates have remained largely unknown. Here, we performed an in vitro screen of the Populus trichocarpa BAHD acyltransferase superfamily (116 genes) using a wheatgerm cell-free translation system and found five enzymes capable of producing monolignol–p-hydroxybenzoates. We then compared the transcript abundance of the five corresponding genes with p-hydroxybenzoate concentrations using naturally occurring unrelated genotypes of P. trichocarpa and revealed a positive correlation between the expression of p-hydroxybenzoyl-CoA monolig-nol transferase (pHBMT1, Potri.001G448000) and p-hydroxybenzoate levels. To test whether pHBMT1 is responsible for the biosynthesis of monolignol–p-hydroxybenzoates, we overexpressed pHBMT1 in hybrid poplar (Populus alba × P. grandidentata) (35S::pHBMT1 and C4H::pHBMT1). Using three complementary analytical methods, we showed that there was an increase in soluble monolignol–p-hydroxybenzoates and cell-wall-bound monolignol–p-hydroxybenzoates in the poplar transgenics. As these pendent groups are ester-linked, saponification releases p-hydroxybenzoate, a precursor to parabens that are used in pharmaceuticals and cosmetics. This identified gene could therefore be used to engineer lignocellulosic biomass with increased value for emerging biorefinery strategies.
Advances in magnetic resonance imaging contrast agents for glioblastoma-targeting theranostics
Authors: Wu Zijun , Dai Lixiong , Tang Ke , Ma Yiqi , Song Bin , Zhang Yanrong , Li Jinxing , Lui Su , Gong Qiyong , Wu Min 
Published: November 2021

AbstractGlioblastoma (GBM) is the most aggressive malignant brain tumour, with a median survival of 3 months without treatment and 15 months with treatment. Early GBM diagnosis can significantly improve patient survival due to early treatment and management procedures. Magnetic resonance imaging (MRI) using contrast agents is the preferred method for the preoperative detection of GBM tumours. However, commercially available clinical contrast agents do not accurately distinguish between GBM, surrounding normal tissue and other cancer types due to their limited ability to cross the blood–brain barrier, their low relaxivity and their potential toxicity. New GBM-specific contrast agents are urgently needed to overcome the limitations of current contrast agents. Recent advances in nanotechnology have produced alternative GBM-targeting contrast agents. The surfaces of nanoparticles (NPs) can be modified with multimodal contrast imaging agents and ligands that can specifically enhance the accumulation of NPs at GBM sites. Using advanced imaging technology, multimodal NP-based contrast agents have been used to obtain accurate GBM diagnoses in addition to an increased amount of clinical diagnostic information. NPs can also serve as drug delivery systems for GBM treatments. This review focuses on the research progress for GBM-targeting MRI contrast agents as well as MRI-guided GBM therapy.
Increased risk of thoracic aortic complications among patients with giant cell arteritis: a nationwide, population-based cohort study
Authors: Therkildsen Philip , de Thurah Annette , Nielsen Berit Dalsgaard , Hansen Ib Tønder , Eldrup Nikolaj , Nørgaard Mette , Hauge Ellen-Margrethe 
Published: November 2021

Abstract

Objective
To assess the risk of aortic aneurysms (AA), aortic dissections (AD) and peripheral arterial disease (PAD) among patients with GCA.

Methods
In this nationwide, population-based cohort study using Danish national health registries, we identified all incident GCA patients ≥50 years between 1996 and 2018 who redeemed three or more prescriptions for prednisolone. Index date was the date of redeeming the third prednisolone prescription. Case definition robustness was checked through sensitivity analysis. We included general population referents matched 1:10 by age, sex and calendar time. Using a pseudo-observation approach, we calculated 5-, 10- and 15-year cumulative incidence proportions (CIP) and relative risks (RR) of AA, AD and PAD with death as a competing risk.

Results
We included 9908 GCA patients and 98 204 referents. The 15-year CIP of thoracic AA, abdominal AA, AD and PAD in the GCA cohort were 1.9% (95% CI 1.5, 2.2), 1.8% (1.4–2.2), 1.0% (0.7–1.2) and 4.8% (4.2–5.3). Compared with the referents, the 15-year RR were 11.2 (7.41–16.9) for thoracic AA, 6.86 (4.13–11.4) for AD, 1.04 (0.83–1.32) for abdominal AA and 1.53 (1.35–1.74) for PAD. Among GCA patients, female sex, age below 70 years and positive temporal artery findings were risk factors for developing thoracic AA. The median time to thoracic AA was 7.5 years (interquartile range 4.4–11.2) with a number needed to be screened of 250 (167–333), 91 (71–111) and 53 (45–67) after 5, 10 and 15 years.

Conclusion
Patients with GCA have a markedly increased risk of developing thoracic AA and AD, but no increased risk of abdominal AA.
Poor Correlation between Diaphragm Thickening Fraction and Transdiaphragmatic Pressure in Mechanically Ventilated Patients and Healthy Subjects
Authors: Poulard Thomas , Bachasson Damien , Fossé Quentin , Niérat Marie-Cécile , Hogrel Jean-Yves , Demoule Alexandre , Gennisson Jean-Luc , Dres Martin 
Published: November 2021

Background
The relationship between the diaphragm thickening fraction and the transdiaphragmatic pressure, the reference method to evaluate the diaphragm function, has not been clearly established. This study investigated the global and intraindividual relationship between the thickening fraction of the diaphragm and the transdiaphragmatic pressure. The authors hypothesized that the diaphragm thickening fraction would be positively and significantly correlated to the transdiaphragmatic pressure, in both healthy participants and ventilated patients.

Methods
Fourteen healthy individuals and 25 mechanically ventilated patients (enrolled in two previous physiologic investigations) participated in the current study. The zone of apposition of the right hemidiaphragm was imaged simultaneously to transdiaphragmatic pressure recording within different breathing conditions, i.e., external inspiratory threshold loading in healthy individuals and various pressure support settings in patients. A blinded offline breath-by-breath analysis synchronously computed the changes in transdiaphragmatic pressure, the diaphragm pressure-time product, and diaphragm thickening fraction. Global and intraindividual relationships between variables were assessed.

Results
In healthy subjects, both changes in transdiaphragmatic pressure and diaphragm pressure-time product were moderately correlated to diaphragm thickening fraction (repeated measures correlation = 0.40, P < 0.0001; and repeated measures correlation = 0.38, P < 0.0001, respectively). In mechanically ventilated patients, changes in transdiaphragmatic pressure and thickening fraction were weakly correlated (repeated measures correlation = 0.11, P = 0.008), while diaphragm pressure-time product and thickening fraction were not (repeated measures correlation = 0.04, P = 0.396). Individually, changes in transdiaphragmatic pressure and thickening fraction were significantly correlated in 8 of 14 healthy subjects (ρ = 0.30 to 0.85, all P < 0.05) and in 2 of 25 mechanically ventilated patients (ρ = 0.47 to 0.64, all P < 0.05). Diaphragm pressure-time product and thickening fraction correlated in 8 of 14 healthy subjects (ρ = 0.41 to 0.82, all P < 0.02) and in 2 of 25 mechanically ventilated patients (ρ = 0.63 to 0.66, all P < 0.01).

Conclusions
Overall, diaphragm function as assessed with transdiaphragmatic pressure was weakly related to diaphragm thickening fraction. The diaphragm thickening fraction should not be used in healthy subjects or ventilated patients when changes in diaphragm function are evaluated.

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Surgical Outcomes of Transposition Surgery for the Correction of Large-Angle Strabismus
Authors: Gokoffski Kimberly Kinga , Lifton Jacob , Xu Benjamin Yixing , Patel Vivek Ravindra 
Published: November 2021

Background:
Many potential surgical options exist to address large-angle deviations and head turns that result from various forms of paralytic strabismus. Muscle transposition surgeries serve as suitable alternatives to simple resection–recessions. Here, we report outcomes of augmented Hummelsheim and X-type transpositions for the correction of large-angle strabismus and provide insights for surgical planning.

Methods:
We performed a retrospective chart review of 40 consecutive patients with strabismus who were treated with an augmented Hummelsheim or X-type transposition surgery at a single academic medical center. Etiologies included cranial nerve palsies (n = 26), monocular elevation palsy (n = 3), Duane syndrome (n = 1), traumatic extraocular muscle damage (n = 8), and chronic progressive external ophthalmoplegia (n = 2). All patients were followed for a minimum of 2 months postsurgery. Logistic regression analyses were performed to assess for predictors of surgical outcome.

Results:
Forty consecutive patients were enrolled in our series. The median preoperative deviation was 46.5Δ (interquartile range [IQR] 35–70). The median postoperative deviation 2 months after surgery was 0.5Δ (IQR 0–9.5), which represented a significant improvement (P < 0.001). Thirty-three patients (82.5%) experienced an improvement in range and/or centration of binocular single vision (BSV). More patients who underwent an augmented Hummelsheim procedure and had a small overcorrection at postoperative day 3 had a favorable result on postoperative month 2 (79%) compared with those that were initially under-corrected (38%). Multiple logistic regressions found larger preoperative deviation (P < 0.005) and esotropia (P < 0.021) to be predictors of a less favorable surgical outcome (C-statistic = 0.83). Subgroup analysis revealed that less, favorable outcome after X-type transposition occurred most frequently in patients undergoing correction of an esodeviation.

Conclusion:
Augmented Hummelsheim transposition techniques offer effective treatment options for paralytic strabismus with esotropic deviations, whereas X-type transpositions are effective for exotropic deviations and deviations from severe inferior rectus damage. In addition to potentially providing a wider field of BSV, improved centration is often achieved.
Neuroradiologic Imaging of Neurologic and Neuro-Ophthalmic Complications of Coronavirus-19 Infection
Authors: Marsiglia Marcela , Chwalisz Bart K. , Maher Mary 
Published: November 2021

Background:
To review the literature and provide a summary of COVID-19–related neurologic and neuro-ophthalmic complications.

Methods:
The currently available literature was reviewed on PubMed and Google Scholar using the following keywords for searches: CNS, Neuro-Ophthalmology, COVID-19, SARS-CoV-2, coronavirus, optic neuritis, pseudotumor cerebri, Acute Disseminated Encephalomyelitis, posterior reversible encephalopathy syndrome (PRES), meningitis, encephalitis, acute necrotizing hemorrhagic encephalopathy, and Guillain–Barré and Miller Fisher syndromes.

Results:
Neuroradiologic findings of neurologic and neuro-ophthalmologic complications in relationship to COVID-19 infection were reviewed. Afferent visual pathway–related disorders with relevant imaging manifestations included fundus nodules on MRI, papilledema and pseudotumor cerebri syndrome, optic neuritis, Acute Disseminated Encephalomyelitis, vascular injury with thromboembolism and infarct, leukoencephalopathy, gray matter hypoxic injury, hemorrhage, infectious meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and PRES. Efferent visual pathway–related complications with relevant imaging manifestations were also reviewed, including orbital abnormalities, cranial neuropathy, Guillain–Barré and Miller Fisher syndromes, and nystagmus and other eye movement abnormalities related to rhombencephalitis.

Conclusion:
COVID-19 can cause central and peripheral nervous system disease, including along both the afferent and efferent components of visual axis. Manifestations of disease and long-term sequela continue to be studied and described. Familiarity with the wide variety of neurologic, ophthalmic, and neuroradiologic presentations can promote prompt and appropriate treatment and continue building a framework to understand the underlying mechanism of disease.
Consonance perception in congenital amusia: behavioral and brain responses to harmonicity and beating cues
Authors: Graves Jackson E. , Pralus Agathe , Fornoni Lesly , Oxenham Andrew J. , Tillmann Barbara , Caclin Anne 
Published: November 2021

AbstractCongenital amusia is a neurodevelopmental disorder characterized by difficulties in the perception and production of music, including the perception of consonance and dissonance, or the judgment of certain combinations of pitches as more pleasant than others. Two perceptual cues for dissonance are inharmonicity (the lack of a common fundamental frequency between components) and beating (amplitude fluctuations produced by close, interacting frequency components). In the presence of inharmonicities or beats, amusics have previously been reported to be insensitive to inharmonicity, but to exhibit normal sensitivity to beats. In the present study, we measured adaptive discrimination thresholds in amusic participants and found elevated thresholds for both cues. We recorded EEG and measured the mismatch negativity (MMN) in evoked potentials to consonance and dissonance deviants in an oddball paradigm. The amplitude of the MMN response was similar overall for amusics and controls, but while control participants showed a stronger MMN to harmonicity cues than to beating cues, amusic participants showed a stronger MMN to beating cues than to harmonicity cues. These findings suggest that initial encoding of consonance cues may be intact in amusia despite impaired behavioral performance, but that the relative weight of non-spectral cues may be increased for amusic individuals.
A copula based topology preserving graph convolution network for clustering of single-cell RNA seq data
Authors: Lall Snehalika , Ray Sumanta , Bandyopadhyay Sanghamitra 
Published: November 2021

AbstractAnnotation of cells in single-cell clustering requires a homogeneous grouping of cell populations. There are various issues in single cell sequencing that effect homogeneous grouping (clustering) of cells, such as small amount of starting RNA, limited per-cell sequenced reads, cell-to-cell variability due to cell-cycle, cellular morphology, and variable reagent concentrations. Moreover, single cell data is susceptible to technical noise, which affects the quality of genes (or features) selected/extracted prior to clustering.Here we introduce sc-CGconv (copula based graph convolution network for single cell clustering), a stepwise robust unsupervised feature extraction and clustering approach that formulates and aggregates cell–cell relationships using copula correlation (Ccor), followed by a graph convolution network based clustering approach. sc-CGconv formulates a cell-cell graph using Ccor that is learned by a graph-based artificial intelligence model, graph convolution network. The learned representation (low dimensional embedding) is utilized for cell clustering. sc-CGconv features the following advantages. a. sc-CGconv works with substantially smaller sample sizes to identify homogeneous clusters. b. sc-CGconv can model the expression co-variability of a large number of genes, thereby outperforming state-of-the-art gene selection/extraction methods for clustering. c. sc-CGconv preserves the cell-to-cell variability within the selected gene set by constructing a cell-cell graph through copula correlation measure. d. sc-CGconv provides a topology-preserving embedding of cells in low dimensional space.The source code and usage information are available at https://github.com/Snehalikalall/CopulaGCNContact:sumanta.ray@cwi.nl
Contingency and selection in mitochondrial genome dynamics
Authors: Nunn Christopher J. , Goyal Sidhartha 
Published: November 2021

AbstractEukaryotic cells contain numerous copies of mitochondrial DNA (mtDNA), allowing for the coexistence of mutant and wild-type mtDNA in individual cells. The fate of mutant mtDNA depends on their relative replicative fitness within cells and the resulting cellular fitness within populations of cells. Yet the dynamics of the generation of mutant mtDNA and features that inform their fitness remain unaddressed. Here we utilize long read single-molecule sequencing to track mtDNA mutational trajectories in Saccharomyces cerevisiae. We show a previously unseen pattern that constrains subsequent excision events in mtDNA fragmentation. We also provide evidence for the generation of rare and contentious non-periodic mtDNA structures that lead to persistent diversity within individual cells. Finally, we show that measurements of relative fitness of mtDNA fit a phenomenological model that highlights important biophysical parameters governing mtDNA fitness. Altogether, our study provides techniques and insights into the dynamics of large structural changes in genomes that may be applicable in more complex organisms.
A booster dose of an inactivated SARS-CoV-2 vaccine increases neutralizing antibodies and T cells that recognize Delta and Omicron variants of concern
Authors: Schultz Bárbara M , Melo-González Felipe , Duarte Luisa F , Gálvez Nicolás MS , Pacheco Gaspar A , Soto Jorge A , Berríos-Rojas Roslye V , González Liliana A , Moreno-Tapia Daniela , Rivera-Pérez Daniela , Ríos Mariana , Vázquez Yaneisi , Hoppe-Elsholz Guillermo , Vallejos Omar P , Iturriaga Carolina , Urzua Marcela , Navarrete María S , Rojas Álvaro , Fasce Rodrigo , Fernández Jorge , Mora Judith , Ramírez Eugenio , Gaete-Argel Aracelly , Acevedo Mónica , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Weiskopf Daniela , Grifoni Alba , Sette Alessandro , Zeng Gang , Meng Weining ,   CoronaVac03CL Study Group, González-Aramundiz José V , González Pablo A , Abarca Katia , Kalergis Alexis M , Bueno Susan M 
Published: November 2021

AbstractBackgroundCoronaVac®is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac®, but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac®on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile.MethodsVolunteers immunized with two doses of CoronaVac®in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose.FindingsWe observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4+T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron.InterpretationOur results show that a booster dose of CoronaVac®increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac®is active against VOC, suggesting an effective protection.
A recurrent circuit links antagonistic cerebellar modules during associative motor learning
Authors: Ohmae Shogo , Ohmae Keiko , Heiney Shane , Subramanian Divya , Medina Javier 
Published: November 2021

ABSTRACTThe neural architecture of the cerebellum is thought to be specialized for performing supervised learning: specific error-related climbing fiber inputs are used to teach sensorimotor associations to small ensembles of Purkinje cells located in functionally distinct modules that operate independently of each other in a purely feedforward manner. Here, we test whether the basic operation of the cerebellum complies with this basic architecture in mice that learned a simple sensorimotor association during eyeblink conditioning. By recording Purkinje cells in different modules and testing whether their responses rely on recurrent circuits, our results reveal three operational principles about the functional organization of the cerebellum that stand in stark contrast to the conventional view: (1) Antagonistic organization, (2) Recurrent network dynamics, and (3) Intermodular communication. We propose that the neural architecture of the cerebellum implements these three operational principles to achieve optimal performance and solve a number of problems in motor control.