bluuebunny/crossref_metadata_2025_split huggingface dataset:
De Novo Mutation Rate Variation and Its Determinants inChlamydomonas
Authors: López-Cortegano Eugenio , Craig Rory J , Chebib Jobran , Samuels Toby , Morgan Andrew D , Kraemer Susanne A , Böndel Katharina B , Ness Rob W , Colegrave Nick , Keightley Peter D 
Published: May 2021

AbstractDe novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo mutations is challenging and is generally restricted to model species, so we have a limited understanding of the evolution of the mutation rate and spectrum between closely related species. Here, we present a mutation accumulation (MA) experiment to study de novo mutation in the unicellular green alga Chlamydomonas incerta and perform comparative analyses with its closest known relative, Chlamydomonas reinhardtii. Using whole-genome sequencing data, we estimate that the median single nucleotide mutation (SNM) rate in C. incerta is μ = 7.6 × 10−10, and is highly variable between MA lines, ranging from μ = 0.35 × 10−10 to μ = 131.7 × 10−10. The SNM rate is strongly positively correlated with the mutation rate for insertions and deletions between lines (r &gt; 0.97). We infer that the genomic factors associated with variation in the mutation rate are similar to those in C. reinhardtii, allowing for cross-prediction between species. Among these genomic factors, sequence context and complexity are more important than GC content. With the exception of a remarkably high C→T bias, the SNM spectrum differs markedly between the two Chlamydomonas species. Our results suggest that similar genomic and biological characteristics may result in a similar mutation rate in the two species, whereas the SNM spectrum has more freedom to diverge.
snpXplorer: a web application to explore human SNP-associations and annotate SNP-sets
Authors: Tesi Niccolo , van der Lee Sven , Hulsman Marc , Holstege Henne , Reinders Marcel J T 
Published: May 2021

AbstractGenetic association studies are frequently used to study the genetic basis of numerous human phenotypes. However, the rapid interrogation of how well a certain genomic region associates across traits as well as the interpretation of genetic associations is often complex and requires the integration of multiple sources of annotation, which involves advanced bioinformatic skills. We developed snpXplorer, an easy-to-use web-server application for exploring Single Nucleotide Polymorphisms (SNP) association statistics and to functionally annotate sets of SNPs. snpXplorer can superimpose association statistics from multiple studies, and displays regional information including SNP associations, structural variations, recombination rates, eQTL, linkage disequilibrium patterns, genes and gene-expressions per tissue. By overlaying multiple GWAS studies, snpXplorer can be used to compare levels of association across different traits, which may help the interpretation of variant consequences. Given a list of SNPs, snpXplorer can also be used to perform variant-to-gene mapping and gene-set enrichment analysis to identify molecular pathways that are overrepresented in the list of input SNPs. snpXplorer is freely available at https://snpxplorer.net. Source code, documentation, example files and tutorial videos are available within the Help section of snpXplorer and at https://github.com/TesiNicco/snpXplorer.
Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response
Authors: Yu Fang , Wei Jiangbo , Cui Xiaolong , Yu Chunjie , Ni Wei , Bungert Jörg , Wu Lizi , He Chuan , Qian Zhijian 
Published: May 2021

Abstract
Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m6A levels that protect genomic integrity of cells in response to ROS.
Common Femoral Artery Access: 2-Dimensional Operative Video
Authors: Darwal Maureen A , Binning Mandy J ,   Endovascular Neurosurgery Research Group (ENRG), Bain Mark , Bendock Bernard , Boulos Alan S , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Replogle Robert , Riina Howard , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan , Spiotta Alex , Sultan Ali , Thomas Ajith , Turner Raymond , Welch Babu , White Jonathan 
Published: May 2021

Abstract
Vascular access for cerebral angiography has traditionally been performed via the common femoral artery. It is crucial to obtain safe access to prevent complications that could lead to limb ischemia, groin hematoma, or retroperitoneal hematoma. This is especially true in neurointervention as many patients are anticoagulated or have received intravenous thrombolytics prior to their intervention. Special attention to anatomic landmarks, both grossly and radiographically, can help to assure safe access. The patient consented for this procedure. This video details rapid but safe femoral artery access in a patient undergoing emergent thrombectomy.
Endoscopic-Assisted Keyhole Resection of a Recurrent Epidermoid Tumor: 2-Dimensional Operative Video
Authors: Essayed Walid I B N , Al-Mefty Ossama 
Published: May 2021

Abstract
Epidermoid tumors are benign lesions. Surgical resection is the only treatment option available for these lesions.
1
The surgical approach should be tailored to the clinical and anatomic findings to achieve radical resection, preferably total removal of the content and the capsule to prevent recurrences.
2
Total resection is frequently possible in de novo lesions using tailored skull base approaches and their combination as well as modern microsurgical techniques, including the endoscope-assisted tools.
2

,

3

Giant recurrent tumors, however, are not amenable for total resection. Hence, the severe adhesions will lead to a higher morbidity as the epidermoid capsule becomes thicker and more fibrous after prior resections attempts.
2

,

4
The extent of the resection should still be safely extended as much as possible to delay the interval between surgeries. Endoscopic techniques are of great help in achieving such results through a keyhole approach when conservative surgery is decided.
3
We present the case of a 69-yr-old male with a past medical history of coronary heart disease, hypertension, hypothyroidism, and recurrent giant epidermoid cyst in the left cerebellopontine angle, with significant compression of the brainstem and extended into Meckel's cave, internal auditory canal, and jugular fossa. He underwent resection in 1983, 2004, and 2012. He presented with worsening gait, and multiple cranial nerves deficits. A minimally invasive approach through a keyhole craniotomy was performed given the age, comorbidity, and multirecurrent nature of his lesion. The patient consented to the intervention and publication of his image. He had a satisfying evacuation of his cyst content with transient facial and lower cranial nerve postoperative worsening.
Resection of Pontine Cavernoma Through the Anterior Transpetrosal Approach: 2-Dimensional Operative Video
Authors: Kadri Paulo A S , Essayed Walid I B N , Al-Mefty Ossama 
Published: May 2021

Abstract
The pons is the most frequent local for brain stem cavernoma.
1
Repeated hemorrhage of brainstem cavernoma is associated with significant and accumulative neurological deficits and thus requires treatment. According to the Swedish Karolinska’s group of radiosurgery, ”it could not be concluded whether GKRS affects the natural course of a CM. The incidence of radiation-induced complications was approximately seven times higher than that expected.”
2
Thus, microsurgical removal has become the mainstay of treatment. In our experience, the following details assist in obtaining favorable outcomes and avoiding postoperative complications
3

,

4
: (a) the entry into the cavernoma based on thorough knowledge of the microanatomy; (b) the detailed study of the images and the presentation of the cavernoma on or near the brain stem surface; (c) the resection of the live cavernous hemangioma and not the mere removal of the multiple aged organized hematomas; (d) the preservation of the associated venous angioma; (e) the direct and shortest access to the lesion provided by a skull base approach; and (f) the use of the available technology, such as intraoperative neuromonitoring and neuroimaging.
We present the case of a 54-yr-old male with recent deterioration in year 2001, past repetitive episodes of gait imbalance, and speech difficulty over a 7-yr period from known pontine cavernoma. The anterior petrosal approach provided superb and direct exposure to the entry at the lateral pons and the cavernoma was totally removed with preservation of the venous angioma. His preoperative neurological deficit rapidly recovered. Patient consented to the procedure and photography.
Images at 3:15 from Kadri et al, The anatomical basis for surgical presercation of temporal muscle. J Neurosurg. 2004;100:517-522, used with permission from JNSPG.
Image at 3:27 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997, with permission.
Year-round monitoring at a Pacific coastal campus reveals similar winter and spring collision mortality and high vulnerability of the Varied Thrush
Authors: De Groot Krista L , Porter Alison N , Norris Andrea R , Huang Andrew C , Joy Ruth 
Published: May 2021

Abstract
Bird–window collisions are a leading cause of direct anthropogenic avian mortality, yet our state of knowledge regarding this threat relies heavily on eastern North American studies. Seasonal patterns of collision mortality may differ along the Pacific coast, and western North American species remain understudied. We therefore surveyed a stratified random sample of 8 buildings for collisions at the University of British Columbia, Vancouver, Canada over 45-day periods during 2 winters, 1 spring, 1 summer, and 1 fall season between January 22, 2015 and March 15, 2017. After accounting for the rate of scavenging and efficiency of observers in finding carcasses, we estimated that 360 collision fatalities (95% CI: 281–486) occurred over 225 days of collision monitoring. Collision mortality was highest in fall, but in contrast to most published research, collision mortality was intermediate in both winter and spring and was lowest in summer. In winter 2017, we performed point-count surveys to assess whether individual species are disproportionately vulnerable to collisions when accounting for population size and found that the Varied Thrush (Ixoreus naevius) was 76.9 times more likely to collide with buildings, relative to average species vulnerability in winter. To our knowledge, this is the first study to report the Varied Thrush as a species that is disproportionately vulnerable to collisions. Further studies are needed to assess the vulnerability of Western North American species and subspecies, and to determine whether similar patterns of seasonal collision mortality are found elsewhere.
Hundreds of weak lensing shear-selected clusters from the Hyper Suprime-Cam Subaru Strategic Program S19A data
Authors: Oguri Masamune , Miyazaki Satoshi , Li Xiangchong , Luo Wentao , Mitsuishi Ikuyuki , Miyatake Hironao , More Surhud , Nishizawa Atsushi J , Okabe Nobuhiro , Ota Naomi , Plazas Malagón Andrés A , Utsumi Yousuke 
Published: May 2021

Abstract
We use the Hyper Suprime-Cam Subaru Strategic Program S19A shape catalog to construct weak lensing shear-selected cluster samples. From aperture mass maps covering ∼510 deg2 created using a truncated Gaussian filter, we construct a catalog of 187 shear-selected clusters that correspond to mass map peaks with signal-to-noise ratio larger than 4.7. Most of the shear-selected clusters have counterparts in optically selected clusters, from which we estimate the purity of the catalog to be higher than 95%. The sample can be expanded to 418 shear-selected clusters with the same signal-to-noise ratio cut by optimizing the shape of the filter function and by combining weak lensing mass maps created with several different background galaxy selections. We argue that dilution and obscuration effects of cluster member galaxies can be mitigated by using background source galaxy samples and adopting a filter function with its inner boundary larger than about 2′. The large samples of shear-selected clusters that are selected without relying on any baryonic tracer are useful for detailed studies of cluster astrophysics and cosmology.
Metabolic engineering provides insight into the regulation of thiamin biosynthesis in plants
Authors: Strobbe Simon , Verstraete Jana , Stove Christophe , Van Der Straeten Dominique 
Published: May 2021

Abstract
Thiamin (or thiamine) is a water-soluble B-vitamin (B1), which is required, in the form of thiamin pyrophosphate, as an essential cofactor in crucial carbon metabolism reactions in all forms of life. To ensure adequate metabolic functioning, humans rely on a sufficient dietary supply of thiamin. Increasing thiamin levels in plants via metabolic engineering is a powerful strategy to alleviate vitamin B1 malnutrition and thus improve global human health. These engineering strategies rely on comprehensive knowledge of plant thiamin metabolism and its regulation. Here, multiple metabolic engineering strategies were examined in the model plant Arabidopsis thaliana. This was achieved by constitutive overexpression of the three biosynthesis genes responsible for B1 synthesis, HMP-P synthase (THIC), HET-P synthase (THI1), and HMP-P kinase/TMP pyrophosphorylase (TH1), either separate or in combination. By monitoring the levels of thiamin, its phosphorylated entities, and its biosynthetic intermediates, we gained insight into the effect of either strategy on thiamin biosynthesis. Moreover, expression analysis of thiamin biosynthesis genes showed the plant’s intriguing ability to respond to alterations in the pathway. Overall, we revealed the necessity to balance the pyrimidine and thiazole branches of thiamin biosynthesis and assessed its biosynthetic intermediates. Furthermore, the accumulation of nonphosphorylated intermediates demonstrated the inefficiency of endogenous thiamin salvage mechanisms. These results serve as guidelines in the development of novel thiamin metabolic engineering strategies.
G2/M-checkpoint activation in fasciata1 rescues an aberrant S-phase checkpoint but causes genome instability
Authors: Eekhout Thomas , Dvorackova Martina , Pedroza Garcia José Antonio , Nespor Dadejova Martina , Kalhorzadeh Pooneh , Van den Daele Hilde , Vercauteren Ilse , Fajkus Jiri , De Veylder Lieven 
Published: May 2021

Abstract
The WEE1 and ATM AND RAD3-RELATED (ATR) kinases are important regulators of the plant intra-S-phase checkpoint; consequently, WEE1KO and ATRKO roots are hypersensitive to replication-inhibitory drugs. Here, we report on a loss-of-function mutant allele of the FASCIATA1 (FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex that suppresses the phenotype of WEE1- or ATR-deficient Arabidopsis (Arabidopsis thaliana) plants. We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. This ATM activation accounts for the telomere erosion and loss of ribosomal DNA that are described for fas1 plants. Knocking out SOG1 in the fas1 wee1 background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint.
A Virtual Reality Meditative Intervention Modulates Pain and the Pain Neuromatrix in Patients with Opioid Use Disorder
Authors: Faraj Mohammed M , Lipanski Nina M , Morales Austin , Goldberg Elimelech , Bluth Martin H , Marusak Hilary A , Greenwald Mark K 
Published: May 2021

Abstract

Objective
Standard of care for opioid use disorder (OUD) includes medication and counseling. However, there is an unmet need for complementary approaches to treat OUD patients coping with pain; furthermore, few studies have probed neurobiological features of pain or its management during OUD treatment. This preliminary study examines neurobiological and behavioral effects of a virtual reality-based meditative intervention in patients undergoing methadone maintenance treatment (MMT).

Design
Prospective, non-blinded, single-arm, 12-week intervention with standardized assessments.

Setting
Academic research laboratory affiliated with an on-site MMT clinic.

Methods
Fifteen (11 female) MMT patients completed a virtual reality, therapist-guided meditative intervention that included breathing and relaxation exercisessessions were scheduled twice weekly. Assessments included functional magnetic resonance imaging (fMRI) of pain neuromatrix activation and connectivity (pre- and post-intervention), saliva cortisol and C-reactive protein (CRP) at baseline and weeks 4, 8 and 12; and self-reported pain and affective symptoms before and after each intervention session.

Results
After each intervention session (relative to pre-session), ratings of pain, opioid craving, anxiety and depression (but not anger) decreased. Saliva cortisol (but not CRP) levels decreased from pre- to post-session. From pre- to post-intervention fMRI assessments, pain task-related left postcentral gyrus (PCG) activation decreased. At baseline, PCG showed positive connectivity with other regions of the pain neuromatrix, but this pattern changed post-intervention.

Conclusions
These preliminary findings demonstrate feasibility, therapeutic promise, and brain basis of a meditative intervention for OUD patients undergoing MMT.
Neural response to monetary and social feedback demonstrates differential associations with depression and social anxiety
Authors: Nelson Brady D , Jarcho Johanna M 
Published: May 2021

Abstract
An aberrant neural response to rewards has been linked to both depression and social anxiety. Most studies have focused on the neural response to monetary rewards, and few have tested different modalities of reward (e.g. social) that are more salient to particular forms of psychopathology. In addition, most studies contain critical confounds, including contrasting positive and negative feedback and failing to disentangle being correct from obtaining positive feedback. In the present study, 204 participants underwent electroencephalography during monetary and social feedback tasks that were matched in trial structure, timing and feedback stimuli. The reward positivity (RewP) was measured in response to correctly identifying stimuli that resulted in monetary win, monetary loss, social like or social dislike feedback. All monetary and social tasks elicited a RewP, which were positively correlated. Across all tasks, the RewP was negatively associated with depression and positively associated with social anxiety. The RewP to social dislike feedback, independent of monetary and social like feedback, was also associated with social anxiety. The present study suggests that a domain-general neural response to correct feedback demonstrates a differential association with depression and social anxiety, but a domain-specific neural response to social dislike feedback is uniquely associated with social anxiety.
Simple, efficient and open-source CRISPR/Cas9 strategy for multi-site genome editing in Populus tremula × alba
Authors: Triozzi Paolo M , Schmidt Henry W , Dervinis Christopher , Kirst Matias , Conde Daniel 
Published: May 2021

Abstract
Although the CRISPR/Cas9 system has been successfully used for crop breeding, its application remains limited in forest trees. Here, we describe an efficient gene editing strategy for hybrid poplar, (Populus tremula × alba INRA clone 717-1B4) based on the Golden Gate MoClo cloning. To test the system efficiency for generating single gene mutants, two single guide RNAs (sgRNAs) were designed and incorporated into the MoClo Tool Kit level 2 binary vector with the Cas9 expression cassette to mutate the SHORT ROOT (SHR) gene. Moreover, we also tested its efficiency for introducing mutations in two genes simultaneously by expressing one sgRNA targeting a single site of the YUC4 gene and the other sgRNA targeting the PLT1 gene. For a robust evaluation of the approach, we repeated the strategy to target the LBD12 and LBD4 genes simultaneously, using an independent construct. We generated hairy roots by Agrobacterium rhizogenes-mediated leaf transformation. Sequencing results confirmed the CRISPR/Cas9-mediated mutation in the targeted sites of PtaSHR. Biallelic and homozygous knockout mutations were detected. A deletion spanning both target sites and small insertions/deletions were the most common mutations. Out of the 22 SHR alleles sequenced, 21 were mutated. The phenotype’s characterization showed that transgenic roots with biallelic mutations for the SHR gene lacked a defined endodermal single cell layer, suggesting a conserved gene function similar to its homolog in Arabidopsis Arabidopsis thaliana (L.) Heynh. Sequencing results also revealed the high efficiency of the system for generating double mutants. Biallelic mutations for both genes in the yuc4/plt1 and lbd12/lbd4 roots were detected in three (yuc4/plt1) and two (lbd12/lbd4) out of four transgenic roots evaluated. A small deletion or a single nucleotide insertion at the single target site was the most common mutations. This CRISPR/Cas9 strategy arises as a rapid, simple and standardized gene-editing tool to evaluate the gene role in essential developmental programs such as radial cell differentiation of poplar roots.