bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant cytoplasmic intron retention is a blueprint for RNA binding protein mislocalization in VCP-related amyotrophic lateral sclerosis
Authors: Tyzack Giulia E , Neeves Jacob , Crerar Hamish , Klein Pierre , Ziff Oliver , Taha Doaa M , Luisier Raphaëlle , Luscombe Nicholas M , Patani Rickie 
Published: March 2021

Abstract
We recently described aberrantly increased cytoplasmic SFPQ intron-retaining transcripts (IRTs) and concurrent SFPQ protein mislocalization as new hallmarks of amyotrophic lateral sclerosis (ALS). However, the generalizability and potential roles of cytoplasmic IRTs in health and disease remain unclear. Here, using time-resolved deep sequencing of nuclear and cytoplasmic fractions of human induced pluripotent stem cells undergoing motor neurogenesis, we reveal that ALS-causing VCP gene mutations lead to compartment-specific aberrant accumulation of IRTs. Specifically, we identify &gt;100 IRTs with increased cytoplasmic abundance in ALS samples. Furthermore, these aberrant cytoplasmic IRTs possess sequence-specific attributes and differential predicted binding affinity to RNA binding proteins. Remarkably, TDP-43, SFPQ and FUS—RNA binding proteins known for nuclear-to-cytoplasmic mislocalization in ALS—abundantly and specifically bind to this aberrant cytoplasmic pool of IRTs. Our data are therefore consistent with a novel role for cytoplasmic IRTs in regulating compartment-specific protein abundance. This study provides new molecular insight into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets.
Travelling waves reveal a dynamic seizure source in human focal epilepsy
Authors: Diamond Joshua M , Diamond Benjamin E , Trotta Michael S , Dembny Kate , Inati Sara K , Zaghloul Kareem A 
Published: March 2021

Abstract
Treatment of patients with drug-resistant focal epilepsy relies upon accurate seizure localization. Ictal activity captured by intracranial EEG has traditionally been interpreted to suggest that the underlying cortex is actively involved in seizures. Here, we hypothesize that such activity instead reflects propagated activity from a relatively focal seizure source, even during later time points when ictal activity is more widespread. We used the time differences observed between ictal discharges in adjacent electrodes to estimate the location of the hypothesized focal source and demonstrated that the seizure source, localized in this manner, closely matches the clinically and neurophysiologically determined brain region giving rise to seizures. Moreover, we determined this focal source to be a dynamic entity that moves and evolves over the time course of a seizure. Our results offer an interpretation of ictal activity observed by intracranial EEG that challenges the traditional conceptualization of the seizure source.
Consciousness among delta waves: a paradox?
Authors: Frohlich Joel , Toker Daniel , Monti Martin M 
Published: March 2021

AbstractA common observation in EEG research is that consciousness vanishes with the appearance of delta (1–4 Hz) waves, particularly when those waves are high amplitude. High amplitude delta oscillations are frequently observed in states of diminished consciousness, including slow wave sleep, anaesthesia, generalized epileptic seizures, and disorders of consciousness, such as coma and the vegetative state. This strong correlation between loss of consciousness and high amplitude delta oscillations is thought to stem from the widespread cortical deactivation that occurs during the ‘down states’ or troughs of these slow oscillations. Recently, however, many studies have reported the presence of prominent delta activity during conscious states, which casts doubt on the hypothesis that high amplitude delta oscillations are an indicator of unconsciousness. These studies include work in Angelman syndrome, epilepsy, behavioural responsiveness during propofol anaesthesia, postoperative delirium, and states of dissociation from the environment such as dreaming and powerful psychedelic states. The foregoing studies complement an older, yet largely unacknowledged, body of literature that has documented awake, conscious patients with high amplitude delta oscillations in clinical reports from Rett syndrome, Lennox-Gastaut syndrome, schizophrenia, mitochondrial diseases, hepatic encephalopathy, and non-convulsive status epilepticus. At the same time, a largely parallel body of recent work has reported convincing evidence that the complexity or entropy of EEG and magnetoencephalographic signals strongly relates to an individual’s level of consciousness. Having reviewed this literature, we discuss plausible mechanisms that would resolve the seeming contradiction between high amplitude delta oscillations and consciousness. We also consider implications concerning theories of consciousness, such as integrated information theory and the entropic brain hypothesis. Finally, we conclude that false inferences of unconscious states can be best avoided by examining measures of electrophysiological complexity in addition to spectral power.
A Review of Dung Beetle Introductions in the Antipodes and North America: Status, Opportunities, and Challenges
Authors: Pokhrel Min R , Cairns Stuart C , Hemmings Zac , Floate Kevin D , Andrew Nigel R 
Published: March 2021

AbstractFollowing the introduction of cattle, exotic dung beetles (Coleoptera: Aphodiidae, Geotrupidae, Scarabaeidae) were imported into the Antipodes (Australia and New Zealand) and North America (primarily the United States) to accelerate the degradation of cattle dung on pastures. The history of dung beetle introductions between the two regions is similar but has not previously been assessed: this is important as new introductions are continuing in the regions. Here, we review these introduction programs, report on their current status, and discuss methodological advances. In doing so, we examine the accidental introduction of exotic (i.e., adventive) species and the contribution of both deliberately introduced and adventive species to endemic dung beetle faunas. Further, we provide a list of pest and parasite species whose populations can be reduced by dung beetle activity. We also identify a combined total of 37 introduced and 47 adventive dung beetle species that have become established in the Antipodes and North America, with exotic species dominating dung beetle assemblages from pasture habitats. Climatic and edaphic matches, the size of founding populations, abiotic and biotic stressors, and the time of year when releases are made are all critical determinants that affect the success of dung beetle introduction programs. Finally, we discuss opportunities, plus the risks and challenges associated with dung beetle introductions. We hope that this review will aid in the success of future introduction programs, either to enhance ecosystem services in areas that they are needed, or potentially to reestablish native species in regions where they have been extirpated.
Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank
Authors: Ai Sizhi , Zhang Jihui , Zhao Guoan , Wang Ningjian , Li Guohua , So Hon-Cheong , Liu Yaping , Chau Steven Wai-Ho , Chen Jie , Tan Xiao , Jia Fujun , Tang Xiangdong , Shi Jie , Lu Lin , Wing Yun-Kwok 
Published: March 2021

Abstract

Aims
Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs.

Methods and results
Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P &lt; 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P &lt; 0.001), and suggestive evidence for atrial fibrillation (P &lt; 0.05). However, genetically predicted long sleep duration was not associated with any CVD.

Conclusion
This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.
Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients
Authors: Andreis Alessandro , Imazio Massimo , Piroli Francesco , Avondo Stefano , Casula Matteo , Paneva Elena , De Ferrari Gaetano Maria 
Published: March 2021

Abstract

Aims
The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD.

Methods and results
A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1–16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56–0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61–0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42–0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30–0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12–0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20–2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02–1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02–2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45–1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71–1.43, I2 = 16%), or other DAEs.

Conclusions
The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.
Negative effects of energy supplementation at peak lactation of sheep can be offset by the addition of Lactobacillus-fermented plant extracts
Authors: Beck Matthew R , Garrett Konagh , Olejar Kenneth J , Maxwell Thomas M R , Bunt Craig R , Greer Andrew E , Gregorini Pablo 
Published: March 2021

Abstract
Energy supplementation may reduce oxidative stress by correcting a negative energy balance, but in some contexts, it has been shown to increase oxidative stress, especially at peak lactation. The current experiment examined if a pelleted energy supplement with or without the addition of Lactobacillus-fermented seaweed or seaweed plus terrestrial plants extracts affected oxidative stress of ewes from late gestation through to weaning and ewe and lamb production from lambing to weaning. Treatments were either no supplement (CON−), a pelleted supplement only (CON+, 100 g/ewe per d), CON+ with seaweed extract only (SWO, 10 mL/ewe per day), or CON+ with seaweed plus an arrangement of terrestrial plant extract (SWP, 10 mL/ewe per d). Ewes (n = 160; mean initial BW = 72.3 ± 9.5 kg [mean ± SD]) were randomized to pastures (n = 4 pastures per treatment with 10 ewes each). After lambing, ewes with twins were reallocated to pastures (n = 3 pastures per treatment with 10 ewes each) according to lambing date. At 4 wk in milk, supplementation tended to reduce total antioxidant status (TAS; P = 0.10) and increased glutathione peroxidase (GPx) activity compared with nonsupplemented ewes (P = 0.04). The addition of seaweed and terrestrial plants extracts to the concentrate, that is, SWO and SWP, increased TAS and reduced GPx activity compared with CON+ (P &lt; 0.01). Supplementation increased milk yield at weeks 4, 6, and 8 of lactation, and protein, lactose, and total milk solids yield at peak lactation (week 4; P &lt; 0.05). The CON− ewes had greater somatic cell count than the supplemented ewes at weeks 4, 8, and 10 of lactation (P = 0.03). Our results suggest that energy supplementation, alone, increases oxidative stress of lactating ewes, which may relate to increased oxidative phosphorylation. Most importantly, these results indicate that in situations where energy supplementation is needed to increase animal performance, negative effects of energy supplementation around peak lactation can be offset by the addition of Lactobacillus-fermented plant extracts (SWO and SWP) to improve antioxidant status.
Evaluation of the Epidemiological Characteristics of the Patients Admitted to Our Clinic as a Result of Electric Shock
Authors: Yiğit Ebral , Şener Bahçe Zeynep 
Published: March 2021

Abstract
Electric shocks (ESs) are common traumas in burn units that require treatment by specialists due to high mortality and morbidity. This study aimed to investigate the demographic and clinical characteristics of patients of ES, complications, and injury-related mortality and morbidity rates. The authors retrospectively analyzed data of 432 ES patients treated at the Gazi Yaşargil Training and Research Hospital Burn Center, Turkey, between January 2010 and December 2020. Of the 432 patients, 92 (21.3%) and 340 (78.7%) sustained high- and low-voltage injuries, respectively. While high-voltage burns were common in January and December, low-voltage burns peaked in September and July. Burn patients were mostly males and were between the ages of 19 and 59 years. The majority of the ES events occurred at home. All four patients who died had suffered high-voltage burns, with two of high-voltage burns (2.17%) requiring amputation. None of the patients with low-voltage burns underwent amputation. High-voltage injuries manifested with larger burn surfaces, longer hospitalization, and more complications. Electrical injuries are largely preventable with simple safety precautions in daily life as well as serious consideration of workplace safety.
Detection of period variations of eclipsing binaries in the Catalina Sky Survey
Authors: Papageorgiou Athanasios , Catelan Márcio , Christopoulou Panagiota-Eleftheria , Drake Andrew J , Djorgovski S G 
Published: March 2021

ABSTRACT
We present 126 eclipsing binary candidates among 4683 Catalina Sky Surveys (CSS) detached and semi-detached eclipsing binary systems (EBs) showing cyclic or quadratic period variations over a 12 yr time span. By using inverse Gaussian profiles of the eclipses coupled with a Markov chain Monte Carlo procedure, times of minima (ToM) were calculated and diagrams with eclipse timing variations (ETVs) were constructed. Numerical tests were performed, involving synthetic EBs with period variations generated by the PHOEBE 2.0 engine and actual data for EBs with well-known period variations from the literature, to verify that the calculation of ToM variations for our CSS systems is reliable. A total of 63 out of the 126 EBs show likely cyclic ETVs, while the remainder present quadratic behaviour instead. Periods, amplitudes, period change rates, and associated errors were determined by using sinusoidal and parabolic models. 12 out of the 63 EBs (19 per cent) that appear to exhibit periodic ETVs are low-mass candidates. Additionally, four out of 126 also have maximum quadrature light variations. The possibility that the cyclic variations are caused by the light traveltime effect due to the presence of a tertiary companion is investigated. The possible nature of the quadratic ETVs is also discussed.
Biochemical impact of a disease-causing Ile67Asn substitution on BOLA3 protein
Authors: Sen Sambuddha , Thompson Zechariah , Wachnowsky Christine , Cleary Sean , Harvey Sophie R , Cowan J A 
Published: March 2021

Abstract
Iron-sulfur (Fe-S) cluster biosynthesis involves the action of a variety of functionally distinct proteins, most of which are evolutionarily conserved. Mutations in these Fe-S scaffold and trafficking proteins can cause diseases such as multiple mitochondrial dysfunctions syndrome (MMDS), sideroblastic anemia, and mitochondrial encephalopathy. Herein, we investigate the effect of Ile67Asn substitution in the BOLA3 protein that results in the MMDS2 phenotype. Although the exact functional role of BOLA3 in Fe-S cluster biosynthesis is not known, the [2Fe-2S]-bridged complex of BOLA3 with GLRX5, another Fe-S protein, has been proposed as a viable intermediary cluster carrier to downstream targets. Our investigations reveal that the Ile67Asn substitution impairs the ability of BOLA3 to bind its physiological partner GLRX5, resulting in a failure to form the [2Fe-2S]-bridged complex. Although no drastic structural change in BOLA3 arises from the substitution, as evidenced by wild-type and mutant BOLA3 1H-15N HSQC and ion mobility native mass spectrometry experiments, this substitution appears to influence cluster reconstitution on downstream proteins leading to the disease phenotype. By contrast, substituted derivatives of the holo homodimeric form of BOLA3 are formed and remain active toward cluster exchange.
INT-Hi-C reveals distinct chromatin architecture in endosperm and leaf tissues ofArabidopsis
Authors: Yadav Vikash Kumar , Santos-González Juan , Köhler Claudia 
Published: March 2021

AbstractHigher-order chromatin structure undergoes striking changes in response to various developmental and environmental signals, causing distinct cell types to adopt specific chromatin organization. High throughput chromatin conformation capture (Hi-C) allows studying higher-order chromatin structure; however, this technique requires substantial amounts of starting material, which has limited the establishment of cell type-specific higher-order chromatin structure in plants. To overcome this limitation, we established a protocol that is applicable to a limited amount of nuclei by combining the INTACT (isolation of nuclei tagged in specific cell types) method and Hi-C (INT-Hi-C). Using this INT-Hi-C protocol, we generated Hi-C data from INTACT purified endosperm and leaf nuclei. Our INT-Hi-C data from leaf accurately reiterated chromatin interaction patterns derived from conventional leaf Hi-C data. We found that the higher-order chromatin organization of mixed leaf tissues and endosperm differs and that DNA methylation and repressive histone marks positively correlate with the chromatin compaction level. We furthermore found that self-looped interacting genes have increased expression in leaves and endosperm and that interacting intergenic regions negatively impact on gene expression in the endosperm. Last, we identified several imprinted genes involved in long-range and trans interactions exclusively in endosperm. Our study provides evidence that the endosperm adopts a distinct higher-order chromatin structure that differs from other cell types in plants and that chromatin interactions influence transcriptional activity.
Development of a modular, biocompatible thiolated gelatin microparticle platform for drug delivery and tissue engineering applications
Authors: Pearce Hannah A , Kim Yu Seon , Watson Emma , Bahrami Kiana , Smoak Mollie M , Jiang Emily Y , Elder Michael , Shannon Tate , Mikos Antonios G 
Published: March 2021

Abstract
The field of biomaterials has advanced significantly in the past decade. With the growing need for high-throughput manufacturing and screening, the need for modular materials that enable streamlined fabrication and analysis of tissue engineering and drug delivery schema has emerged. Microparticles are a powerful platform that have demonstrated promise in enabling these technologies without the need to modify a bulk scaffold. This building block paradigm of using microparticles within larger scaffolds to control cell ratios, growth factors and drug release holds promise. Gelatin microparticles (GMPs) are a well-established platform for cell, drug and growth factor delivery. One of the challenges in using GMPs though is the limited ability to modify the gelatin post-fabrication. In the present work, we hypothesized that by thiolating gelatin before microparticle formation, a versatile platform would be created that preserves the cytocompatibility of gelatin, while enabling post-fabrication modification. The thiols were not found to significantly impact the physicochemical properties of the microparticles. Moreover, the thiolated GMPs were demonstrated to be a biocompatible and robust platform for mesenchymal stem cell attachment. Additionally, the thiolated particles were able to be covalently modified with a maleimide-bearing fluorescent dye and a peptide, demonstrating their promise as a modular platform for tissue engineering and drug delivery applications.