bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase‐amplitude coupling profiles differ in frontal and auditory cortices of bats
Authors: García‐Rosales Francisco , López‐Jury Luciana , González‐Palomares Eugenia , Cabral‐Calderín Yuranny , Kössl Manfred , Hechavarria Julio C. 
Published: September 2020

AbstractNeural oscillations are at the core of important computations in the mammalian brain. Interactions between oscillatory activities in different frequency bands, such as delta (1–4 Hz), theta (4–8 Hz) or gamma (>30 Hz), are a powerful mechanism for binding fundamentally distinct spatiotemporal scales of neural processing. Phase‐amplitude coupling (PAC) is one such plausible and well‐described interaction, but much is yet to be uncovered regarding how PAC dynamics contribute to sensory representations. In particular, although PAC appears to have a major role in audition, the characteristics of coupling profiles in sensory and integration (i.e. frontal) cortical areas remain obscure. Here, we address this question by studying PAC dynamics in the frontal‐auditory field (FAF; an auditory area in the bat frontal cortex) and the auditory cortex (AC) of the bat Carollia perspicillata. By means of simultaneous electrophysiological recordings in frontal and auditory cortices examining local‐field potentials (LFPs), we show that the amplitude of gamma‐band activity couples with the phase of low‐frequency LFPs in both structures. Our results demonstrate that the coupling in FAF occurs most prominently in delta/high‐gamma frequencies (1‐4/75‐100 Hz), whereas in the AC the coupling is strongest in the delta‐theta/low‐gamma (2‐8/25‐55 Hz) range. We argue that distinct PAC profiles may represent different mechanisms for neuronal processing in frontal and auditory cortices, and might complement oscillatory interactions for sensory processing in the frontal‐auditory cortex network.
The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers
Authors: Kruijt N. , van den Bersselaar L. R. , Kamsteeg E. J. , Verbeeck W. , Snoeck M. M. J. , Everaerd D. S. , Abdo W. F. , Jansen D. R. M. , Erasmus C. E. , Jungbluth H. , Voermans N. C. 
Published: September 2020

Background and purposeRhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility.MethodsWe performed a retrospective single‐center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l.ResultsAnoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2).ConclusionThese findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next‐generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified.
Cardiovascular disease, psychiatric diagnosis and sex differences in the multistep hypothesis of amyotrophic lateral sclerosis
Authors: Garton F. C. , Trabjerg B. B. , Wray N. R. , Agerbo E. 
Published: September 2020

Background and purposeAmyotrophic lateral sclerosis (ALS) risk increases with age, and a linear log‐incidence and log‐age relationship is interpreted to suggest that five to six factors are involved in disease onset. The factors remain unidentified, except that fewer steps are predicted for those carrying a known ALS‐causing mutation.MethodsMen with a psychiatric disorder or cardiovascular disease (CVD) diagnosis have an increased relative risk of ALS. Using the Danish population registries and ALS diagnosis years 1980 to 2017, we tested whether these factors would decrease the predicted steps to disease.ResultsConsistent with previous reports, we find a linear log‐incidence and log‐age ALS‐onset relationship (n = 4385, regression coefficient b = 4.6, 95% confidence interval [CI]: 4.3–4.9, R2 = 0.99). This did not differ when considering ALS cases with a prior psychiatric diagnosis (n = 391, b = 4.6, 95% CI: 4.0–5.1) Surprisingly, it was higher (+1.5 steps, P = 2.3 × 10−5) for those with a prior CVD diagnosis (n = 901, b = 6.1, 95% CI: 5.4–6.8). To control for competing risk of death, a test to investigate if this effect was maintained in those with CVD in the population demonstrated an increased baseline risk and fewer steps to disease (b = 1.8, 95% CI: 1.2–2.3, P = 4.6 × 10−21), which consistent with a positive association of CVD and ALS. Assessing sex differences, our data and meta‐analyses (n = 22 495) support half a step fewer for men (−0.4, 95% CI: ±0.24, P = 0.00031) without support for contributing differences explained by menopause.ConclusionsAny factor associated with ALS disease onset may be relevant for understanding disease pathogenesis and/or counselling. Modelling disease incidence with age demonstrates some insight into relevant risk factors; however, the outcome can differ if competing risks are considered.
Cardiac sources of cerebral embolism in people with migraine
Authors: De Giuli V. , Grassi M. , Locatelli M. , Gamba M. , Morotti A. , Bonacina S. , Mazzoleni V. , Pezzini D. , Magoni M. , Monastero R. , Padovani A. , Pezzini A. 
Published: September 2020

Background and purposeWhether the reported association between migraine with aura (MA) and cardioembolic stroke may be explained by a higher rate of atrial fibrillation (AF) or by other potential cardiac sources of cerebral embolism remains to be determined.MethodsIn the setting of a single centre cohort study of consecutive patients with acute brain ischaemia stratified by migraine status, the association between AF as well as patent foramen ovale (PFO) and migraine was explored.ResultsIn all, 1738 patients (1017 [58.5%] men, mean age 67.9 ± 14.9 years) qualified for the analysis. Aging was inversely associated with migraine, whilst women had a >3‐fold increased disease risk (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.58–5.66). No association between AF and history of migraine or its pathogenic subtypes was detected. Conversely, migraine was associated with PFO, both in the entire cohort (OR 1.84, 95% CI 1.07–3.16) and in patients aged ≤55 years (OR 2.21, 95% CI 1.16–4.22). This association was significant for MA (OR 2.92, 95% CI 1.32–6.45 in the entire cohort; OR 2.92, 95% CI 1.15–7.41 in patients aged ≤55 years) and in women (OR 8.23, 95% CI 2.06–32.77), but not for migraine without aura.ConclusionsIn patients with brain ischaemia migraine is not associated with AF. Conversely, there is a probable relation between migraine, especially MA, and PFO in patients who are younger and have a more favourable vascular risk factor profile, and in women.
Exercise‐associated rhythm disturbances in poorly performing Thoroughbreds: risk factors and association with racing performance
Authors: Marr Celia M. , Franklin Samantha , Garrod Georgie , Wylie Claire , Smith Lewis , Dukes‐McEwan Jo , Bright Jan , Allen Kate 
Published: September 2020

AbstractBackgroundExercise‐associated cardiac rhythm disturbances are common, but there is a lack of evidence‐based criteria on which to distinguish clinically relevant rhythm disturbances from those that are not.ObjectivesTo describe and characterise rhythm disturbances during clinical exercise testing; to explore potential risk factors for these rhythm disturbances and to determine whether they influenced future racing.Study designRetrospective cohort using a convenience sample.MethodsMedical records were reviewed from two clinical services to identify horses with poor performance and/or respiratory noise with both exercise endoscopy and electrocardiography results. Respiratory and ECG findings recorded by the attending clinicians were described, and for polymorphic ventricular rhythms (n = 12), a consensus team agreed the final rhythm characterisation. Several statistical models analysing risk factors were built and racing records were reviewed to compare horses with and without rhythm disturbance.ResultsOf 245 racehorses, 87 (35.5%) had no ectopic/re‐entrant rhythms, 110 (44.9%) had isolated premature depolarisations during sinus rhythm and 48 (19.6%) horses had complex tachydysrrythmias. Rhythm disturbances were detected during warm‐up in 20 horses (8.2%); during gallop in 61 horses (24.9%) and during recovery in 124 horses (50.6%). Most complex rhythm events occurred during recovery, but there was one horse with a single couplet during gallop and another with a triplet during gallop. Fifteen horses (one with frequent isolated premature depolarisations and 14 complex rhythms) were considered by clinicians to be potentially contributing to poor performance. Treadmill exercise tests, the presence of exercise‐associated upper respiratory tract obstructions and National Hunt racehorses were associated with rhythm disturbances. The proportion of horses racing again after diagnosis (82%) was similar in all groups and univariable analysis revealed no significant associations between subsequent racing and the presence of any ectopic/re‐entrant rhythm, or the various sub‐groups based on phase of exercise in which this was detected.Main limitationsReliance on retrospective data collection from medical records with no control group. Exercise ECGs were collected using only 1 or 2 leads. Variables examined as risk factors could be considered to be inter‐related and our sub‐groups were small.ConclusionsThis study confirms a high prevalence of cardiac rhythm disturbances, including complex ectopic/re‐entrant rhythms, in poorly performing racehorses. Detection of rhythm disturbances may vary with exercise test conditions and exercise‐associated upper respiratory tract obstructions increase the risk of rhythm disturbances.
Markers for Ca++‐induced terminal differentiation of keratinocytes in vitro under defined conditions
Authors: Jeriha Jakob , Kolundzic Nikola , Khurana Preeti , Gordon Mitch , Celli Anna , Mauro Theodora M. , Ilic Dusko 
Published: September 2020

AbstractDifferentiation of normal human keratinocytes (NHK) grown in vitro as a monolayer to confluency can be triggered with an acute increase in concentration of extracellular Ca++. Over several days, induced by Ca++, the cells form pseudostratified sheets that somewhat resemble the basic organization of the intact skin. This experimental system is widely used in studies of keratinocyte biology and skin pathology. However, expression pattern of the genes considered as markers for cells in specific layers of epidermis in vivo does not always match the specific pattern observed in vitro and might lead to misinterpretation of data. Here, we demonstrate that among 18 markers of terminally differentiated keratinocytes of stratum granulosum (SG) and stratum corneum (SC) in vivo, only four (CDSN, KPRP, LCE1C and SPRR4) have reproduced their expression pattern in vitro. Our data suggest that findings based on two‐dimensional (2D) Ca++‐induced terminal differentiation of NHK in vitro should be subjected to additional scrutiny before conclusions could be made and, if possible, verified in other experimental system that might more faithfully represent the in vivo microenvironment.
The PI3Kγ/AKT signaling pathway mediates peripheral antinociceptive action of dipyrone
Authors: Cecílio Nerry T. , Souza Guilherme R. , Alves‐Filho Jose C. , Cunha Fernando Q. , Cunha Thiago M. 
Published: September 2020

AbstractDipyrone (DIP), also known as metamizole, is an over‐the‐counter analgesic used in Europe and Latin America. Evidence suggesting that inflammatory pain attenuation by DIP is associated with a direct impact on peripheral primary nociceptive neurons through the stimulation of nitric oxide signaling pathway. However, the molecular mechanism by which DIP activates this pathway remains unknown. The PI3Kγ/AKT signaling cascade activation is one of the well‐known molecular mechanisms that promote nitric oxide production in sensory neurons. Herein, we investigated the role of the PI3Kγ/AKT signaling cascade in the context of peripheral analgesic effect of DIP. DIP was administered into PGE2 pre‐sensitized paws of rats and mechanical hyperalgesia was determined using electronic von Frey test after 1 h. Nonselective or selective pharmacological inhibitors of PI3Kγ and AKT were also administered in DIP‐treated rats under paws sensitized with PGE2. Intraplantar injection of DIP attenuated PGE2‐induced hyperalgesia in a dose‐dependent manner. Treatment with nonselective (wortmannin or LY294002) or selective (AS605240) pharmacological inhibitors of PI3Kγ reduced the peripheral antihypernociceptive effect of DIP. Consistently, AKT selective inhibitor also reversed analgesic DIP effects. Corroborating these data, we found that DIP induced AKT phosphorylation in cultured dorsal root ganglion neurons, which was prevented in the presence of PI3Kγ selective inhibitor. Taken together, these findings provide evidence that peripheral analgesic effect of DIP is dependent on the activation of PI3Kγ/AKT signaling pathway.
Vitamin D to prevent COVID‐19: recommendations for the design of clinical trials
Authors: Camargo Carlos A. , Martineau Adrian R. 
Published: September 2020

The coronavirus disease 2019 (COVID‐19) pandemic has focused attention on the potential role of vitamin D supplementation to prevent COVID‐19. In this issue, Merzon and colleagues report epidemiologic data on the vitamin D status of 7807 individuals and their risk of developing COVID‐19. In multivariable analyses, low vitamin D status was associated with increased risk of both COVID‐19 infection and hospitalization. The authors call for clinical trials of vitamin D supplementation. In this Commentary, we discuss some of the challenges of vitamin D research and provide recommendations for the design of randomized controlled trials of vitamin D supplementation to prevent COVID‐19.Comment on: https://doi.org/10.1111/febs.15495
Phosphorylated full‐length Tau interacts with 14‐3‐3 proteins via two short phosphorylated sequences, each occupying a binding groove of 14‐3‐3 dimer
Authors: Neves João Filipe , Petrvalská Olivia , Bosica Francesco , Cantrelle François‐Xavier , Merzougui Hamida , O'Mahony Gavin , Hanoulle Xavier , Obšil Tomáš , Landrieu Isabelle 
Published: September 2020

Protein–protein interactions (PPIs) remain poorly explored targets for the treatment of Alzheimer’s disease. The interaction of 14‐3‐3 proteins with Tau was shown to be linked to Tau pathology. This PPI is therefore seen as a potential target for Alzheimer’s disease. When Tau is phosphorylated by PKA (Tau‐PKA), several phosphorylation sites are generated, including two known 14‐3‐3 binding sites, surrounding the phosphorylated serines 214 and 324 of Tau. The crystal structures of 14‐3‐3 in complex with peptides surrounding these Tau phosphosites show that both these motifs are anchored in the amphipathic binding groove of 14‐3‐3. However, in the absence of structural data with the full‐length Tau protein, the stoichiometry of the complex or the interface and affinity of the partners is still unclear. In this work, we addressed these points, using a broad range of biophysical techniques. The interaction of the long and disordered Tau‐PKA protein with 14‐3‐3σ is restricted to two short sequences, containing phosphorylated serines, which bind in the amphipathic binding groove of 14‐3‐3σ. Phosphorylation of Tau is fundamental for the formation of this stable complex, and the affinity of the Tau‐PKA/14‐3‐3σ interaction is in the 1–10 micromolar range. Each monomer of the 14‐3‐3σ dimer binds one of two different phosphorylated peptides of Tau‐PKA, suggesting a 14‐3‐3/Tau‐PKA stoichiometry of 2 : 1, confirmed by analytical ultracentrifugation. These results contribute to a better understanding of this PPI and provide useful insights for drug discovery projects aiming at the modulation of this interaction.
Oral proficiency levels of first‐year entering college students with and without Advanced Placement scores
Authors: Bernhardt Elizabeth B. , Leffell Cici M. 
Published: September 2020

AbstractThough considerable professional discussion has focused on the integration of K–16 curricula, the level of oral proficiency with which students enter college and how that the entry level relates to college programs remains untested. The entry landscape is varied, complexified by the diverse curricula that students experience, in particular within Advanced Placement (AP) programs. The present study probes the oral proficiency levels of 2071 Spanish learners and 712 French learners. The data indicate a significant difference between the oral proficiency levels of students entering college with and without an AP score, but suggest that the difference is only one sublevel higher on the American Council on the Teaching of Foreign Languages' oral proficiency scale, from intermediate mid to intermediate high on average. The paper discusses the implications of these levels, questioning whether they meet the values of the profession, whether students with these levels are prepared for study in literature programs, and whether an investment in AP programs is prudent.
Using climate‐driven leaf phenology and growth to improve predictions of gross primary productivity in North American forests
Authors: Fang Jing , Lutz James A. , Wang Leibin , Shugart Herman H. , Yan Xiaodong 
Published: September 2020

AbstractForest ecosystems are an important sink for terrestrial carbon sequestration. Hence, accurate modeling of the intra‐ and interannual variability of forest photosynthetic productivity remains a key objective in global biology. Applying climate‐driven leaf phenology and growth in models may improve predictions of the forest gross primary productivity (GPP). We used a dynamic non‐structural carbohydrates (NSC) model (FORCCHN2) that couples leaf development and phenology to investigate the relationships among photosynthesis and environmental factors. FORCCHN2 simulates spring and autumn phenological events from heat and chilling, respectively. Leaf area index data from satellites along with climate data estimated localized phenological parameters. NSC limitation, immediate temperature, accumulated heat, and growth potential comprised a daily leaf‐growth model. Functionally, leaf growth was decoupled from photosynthesis. Leaf biomass determined overall photosynthetic production. We compared this model with outputs of the other six terrestrial biospheric models and with observations from the North American Carbon Program Site Interim Synthesis in 18 forest sites. This model improved the predicted performance of yearly GPP with a 57%–210% increase in correlation (median) and up to a 102% reduction in biases (median), compared to three prognostic models and three prescribed models. At the North America continental scale, the model predicted the average annual GPP of 7.38 Pg C/year from forest ecosystems during 1985–2016. The results showed an increasing trend of GPP in North America (1.0 Pg C/decade). The inclusion of climate‐driven phenology and growth has a significant potential for improving dynamic vegetation models, and promotes a further understanding of the complex relationship between environment and photosynthesis.
Evolutionary principles and genetic considerations for guiding conservation interventions under climate change
Authors: Gaitán‐Espitia Juan D. , Hobday Alistair J. 
Published: September 2020

AbstractImpacts of climate change are apparent in natural systems around the world. Many species are and will continue to struggle to persist in their current location as their preferred environment changes. Traditional conservation efforts aiming to prevent local extinctions have focused on two aspects that theoretically enhance genetic diversity—population connectivity and population size—through ‘passive interventions’ (such as protected areas and connectivity corridors). However, the exceptionally rapid loss of biodiversity that we are experiencing as result of anthropogenic climate change has shifted conservation approaches to more ‘active interventions’ (such as rewilding, assisted gene flow, assisted evolution, artificial selection, genetic engineering). We integrate genetic/genomic approaches into an evolutionary biology framework in order to discuss with scientists, conservation managers and decision makers about the opportunities and risks of interventions that need careful consideration in order to avoid unwanted evolutionary outcomes.
Climate‐ versus geographic‐dependent patterns in the spatial distribution of macroinvertebrate assemblages in New World depressional wetlands
Authors: Stenert Cristina , Pires Mateus M. , Epele Luis B. , Grech Marta G. , Maltchik Leonardo , McLean Kyle I. , Mushet David M. , Batzer Darold P. 
Published: September 2020

AbstractAnalyses of biota at lower latitudes may presage impacts of climate change on biota at higher latitudes. Macroinvertebrate assemblages in depressional wetlands may be especially sensitive to climate change because weather‐related precipitation and evapotranspiration are dominant ecological controls on habitats, and organisms of depressional wetlands are temperature‐sensitive ectotherms. We aimed to better understand how wetland macroinvertebrate assemblages were structured according to geography and climate. To do so, we contrasted aquatic‐macroinvertebrate assemblage structure (family level) between subtropical and temperate depressional wetlands of North and South America using presence–absence data from 264 of these habitats across the continents and more‐detailed relative‐abundance data from 56 depressional wetlands from four case‐study locations (North Dakota and Georgia in North America; southern Brazil and Argentinian Patagonia in South America). Both data sets roughly partitioned wetland numbers equally between the two climatic zones and between the continents. We used ordination methods (PCA and NMDS) and tests of multivariate dispersion (PERMDISP) to assess the distribution and the homogeneity in variation in the composition of macroinvertebrate assemblages across climates and continents, respectively. We found that macroinvertebrate assemblage structures in the subtropical depressional wetlands of North and South America were similar to each other (at the family level), while assemblages in the North and South American temperate wetlands were unique from the subtropics, and from each other. Tests of homogeneity of multivariate dispersion indicated that family‐level assemblage structures were more homogeneous in wetlands from the subtropical than the temperate zones. Our study suggests that ongoing climate change may result in the homogenization of macroinvertebrate assemblage structures in temperate zones of North and South America, with those assemblages becoming enveloped by assemblages from the subtropics. Biotic homogenization, more typically associated with other kinds of anthropogenic factors, may also be affected by climate change.