bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty Shocks as Second-Moment News Shocks
Authors: Berger David , Dew-Becker Ian , Giglio Stefano 
Published: February 2019

Abstract
We provide evidence on the relationship between aggregate uncertainty and the macroeconomy. Identifying uncertainty shocks using methods from the news shocks literature, the analysis finds that innovations in realized stock market volatility are robustly followed by contractions, while shocks to forward-looking uncertainty have no significant effect on the economy. Moreover, investors have historically paid large premia to hedge shocks to realized but not implied volatility. A model in which fundamental shocks are skewed left can match those facts. Aggregate volatility matters, but it is the realization of volatility, rather than uncertainty about the future, that has been associated with declines.
An Early Developmental Marker of Deficit versus Nondeficit Schizophrenia
Authors: Kirkpatrick Brian , Gürbüz Oflezer Özlem , Delice Arslan Mehtap , Hack Gary , Fernandez-Egea Emilio 
Published: February 2019

Abstract
People with schizophrenia and primary negative symptoms (deficit schizophrenia) differ from those without such symptoms (nondeficit schizophrenia) on risk factors, course of illness, other signs and symptoms, treatment response, and biological correlates. These differences suggest that the 2 groups may also have developmental differences. A previous study found that people with schizophrenia have a wider palate than comparison subjects. We tested the hypothesis that those with deficit and nondeficit schizophrenia would differ on palate width. A dentist made blinded measurements of palate shape in deficit (N = 21) and nondeficit (N = 25) patients and control subjects (N = 127), matched for age and gender. The deficit group had significantly wider palates than either nondeficit or control subjects (respective means [standard deviation] 37.5 [3.9], 33.7 [3.1], and 34.0 [2.9]; P < .001 for both deficit/nondeficit and deficit/control comparisons, respective effect sizes 1.08 and 1.01). The nondeficit/control difference in width was not significant (P = .83), and there were no significant group differences in length or depth. The power to detect a nondeficit/control difference in width equal in size to that of the deficit/control difference in width (3.5 mm) was 0.99 and 0.92 for a 2.0-mm difference. This difference in palate width may reflect a divergence in development between deficit and nondeficit patients that occurs by the early second trimester and is consistent with the hypothesis that deficit schizophrenia is a separate disease within the syndrome of schizophrenia.
Obstructive sleep apnea and longitudinal Alzheimer’s disease biomarker changes
Authors: Bubu Omonigho M , Pirraglia Elizabeth , Andrade Andreia G , Sharma Ram A , Gimenez-Badia Sandra , Umasabor-Bubu Ogie Q , Hogan Megan M , Shim Amanda M , Mukhtar Fahad , Sharma Nidhi , Mbah Alfred K , Seixas Azizi A , Kam Korey , Zizi Ferdinand , Borenstein Amy R , Mortimer James A , Kip Kevin E , Morgan David , Rosenzweig Ivana , Ayappa Indu , Rapoport David M , Jean-Louis Girardin , Varga Andrew W , Osorio Ricardo S 
Published: February 2019

Abstract

Study Objectives
To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aβ42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) elderly.

Methods
Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aβ42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA.

Results
In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aβ42 levels (B = −2.71, 95% CI = −3.11, −2.35 and B = −2.62, 95% CI = −3.23, −2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA− participants. No significant variations in the biomarker changes over time were seen in the AD group.

Conclusions
In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.
In silico screen identifies a new Toxoplasma gondii mitochondrial ribosomal protein essential for mitochondrial translation
Authors: Lacombe Alice , Maclean Andrew E. , Ovciarikova Jana , Tottey Julie , Sheiner Lilach 
Published: February 2019

SummaryApicomplexan parasites cause diseases such as malaria and toxoplasmosis. The apicomplexan mitochondrion shows striking differences from common model organisms, including in fundamental processes such as mitochondrial translation. Despite evidence that mitochondrial translation is essential for parasites survival, it is largely understudied. Progress has been restricted by the absence of functional assays to detect apicomplexan mitochondrial translation, a lack of knowledge of proteins involved in the process and the inability to identify and detect mitoribosomes.Using mRNA expression patterns, 279 candidate mitochondrial housekeeping components were identified in Toxoplasma. 11 were validated, including the mitoribosomal small subunit protein 35 (TgmS35). TgmS35 tagging enabled the detection of a macromolecular complex corresponding to the mitoribosomal small subunit for the first time in apicomplexans. A new analytical pipeline detected defects in mitochondrial translation upon TgmS35 depletion, while other mitochondrial functions remain unaffected. Our work lays a foundation for the study of apicomplexan mitochondrial translation.Abbreviated summaryThe apicomplexan mitochondrion is divergent and essential yet poorly studied. Mitochondrial translation is predicted to utilize ribosomes assembled from fragmented rRNA but this was never shown. Knowing the mitochondrial protein content is critical for these studies. We identified 11 new mitochondrial proteins via in-silico searches. Tagging and depletion of a mitoribosomal small subunit protein enabled the first detection of a macromolecular ribosomal complex, and provided proof of principle for our new mitochondrial translation analytic pipeline.
Altered brain morphology in boys with attention-deficit/hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder
Authors: Vetter Nora C. , Backhausen Lea L. , Buse Judith , Roessner Veit , Smolka Michael N. 
Published: February 2019

AbstractAbout 50% of ADHD patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure ADHD (ADHD-only) and ADHD with comorbid ODD/CD (ADHD+ODD/CD) and only focused on specific measures (e.g. volumetric differences), leading to inconsistent results. Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning different indices, i.e. subcortical and cortical volume, cortical thickness, and surface area. We aimed to disentangle disorder-specific etiological contributions regarding structural brain alterations and expected similar and differential alterations between the patient groups.We acquired structural images from an adolescent sample range (11 to 17 years) matched with regard to age, pubertal status, and IQ - including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing boys (TD). We analyzed subcortical and cortical volume, cortical thickness, and surface area with FreeSurfer.We found reductions in total gray matter and right cerebellar volume as well as total surface area for both patient groups. For the left cerebellar volume ADHD+ODD/CD, but not ADHD only differed from TD. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged.Overall, we found similarities but also differences in brain morphology between the two related disorders. Patients with a “double burden” seem to be even more affected than patients with pure ADHD.
Characterization of the genetic architecture underlying eye size variation withinDrosophila melanogasterandDrosophila simulans
Authors: Gaspar Pedro , Arif Saad , Sumner-Rooney Lauren , Kittelmann Maike , Bodey Andrew J. , Stern David L. , Nunes Maria D. S. , McGregor Alistair P. 
Published: February 2019

AbstractThe compound eyes of insects exhibit striking variation in size, reflecting adaptation to different lifestyles and habitats. However, the genetic and developmental bases of variation in insect eye size is poorly understood, which limits our understanding of how these important morphological differences evolve. To address this, we further explored natural variation in eye size within and between four species of theDrosophila melanogasterspecies subgroup. We found extensive variation in eye size among these species, and flies with larger eyes generally had a shorter inter-ocular distance andvice versa. We then carried out quantitative trait loci (QTL) mapping of intra-specific variation in eye size and inter-ocular distance in bothD. melanogasterandD. simulans.This revealed that different genomic regions underlie variation in eye size and inter-ocular distance in both species, which we corroborated by introgression mapping inD. simulans. This suggests that although there is a trade-off between eye size and inter-ocular distance, variation in these two traits is likely to be caused by different genes and so can be genetically decoupled. Finally, although we detected QTL for intra-specific variation in eye size at similar positions inD. melanogasterandD. simulans, we observed differences in eye fate commitment between strains of these two species. This indicates that different developmental mechanisms and therefore, most likely, different genes contribute to eye size variation in these species. Taken together with the results of previous studies, our findings suggest that the gene regulatory network that specifies eye size has evolved at multiple genetic nodes to give rise to natural variation in this trait within and among species.
Protection of phage applications in crop production: a patent landscape
Authors: Holtappels D. , Lavigne R. , Huys I. , Wagemans J. 
Published: February 2019

AbstractIn agriculture, the prevention and treatment of bacterial infections represents an increasing challenge. Traditional (chemical) methods have been restricted to ensure public health and limit the occurrence of resistant strains. Bacteriophages could be a sustainable alternative. A major hurdle towards the commercial implementation of phage-based biocontrol strategies concerns aspects of regulation and intellectual property protection. Within this study, two datasets have been composed to analyze both scientific publications and patent documents and to get an idea on the focus of R&D by means of an abstract and claim analysis. 137 papers and 49 patent families were found searching public databases, their numbers increasing over time. Within this dataset, the majority of the patent documents were filed by non-profit organizations in Asia. There seems to be a good correlation between the papers and patent documents in terms of targeted bacterial genera. Furthermore, granted patents seem to claim rather broad and cover methods of treatment. This review shows that there is indeed a growing publishing and patenting activity concerning phage biocontrol. Targeted research is needed to further stimulate the exploration of phages within integrated pest management strategies and to deal with bacterial infections in crop production.
Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly
Authors: Bridavsky Mike , Kuhl Heiner , Woodruff Arthur , Kornak Uwe , Timmermann Bernd , Mages Norbert ,   99 Lives Consortium, Lupiáñez Darío G. , Symmons Orsolya , Ibrahim Daniel M. 
Published: February 2019

AbstractRare diseases and their underlying molecular causes are often poorly studied, posing challenges for patient diagnosis and prognosis. The development of next-generation sequencing and its decreasing costs promises to alleviate such issues by supplying personal genomic information at a moderate price. Here, we used crowdfunding as an alternative funding source to sequence the genome of Lil BUB, a celebrity cat affected by rare disease phenotypes characterized by supernumerary digits, osteopetrosis and dwarfism, all phenotypic traits that also occur in human patients. We discovered that Lil BUB is affected by two distinct mutations: a heterozygous mutation in the limb enhancer of the Sonic hedgehog gene, previously associated with polydactyly in Hemingway cats; and a novel homozygous frameshift deletion affecting the TNFRSF11A (RANK) gene, which has been linked to osteopetrosis in humans. We communicated the progress of this project to a large online audience, detailing the ‘inner workings’ of personalized whole genome sequencing with the aim of improving genetic literacy. Our results highlight the importance of genomic analysis in the identification of disease-causing mutations and support crowdfunding as a means to fund low-budget projects and as a platform for scientific communication.
Centrosomes control kinetochore-fiber plus-end dynamics via HURP to ensure symmetric divisions
Authors: Dudka Damian , Liaudet Nicolas , Vassal Hélène , Meraldi Patrick 
Published: February 2019

SUMMARYDuring mitosis centrosomes can affect the length of kinetochore-fibers (k-fibers) and the stability of kinetochore-microtubule attachments, implying that they regulate k-fiber dynamics. The exact cellular and molecular mechanisms by which centrosomes regulate k-fibers remain, however, unknown. Here, we created human non-cancerous cells with only one centrosome to investigate these mechanisms. Such cells formed highly asymmetric bipolar spindles that resulted in asymmetric cell divisions. K-fibers in acentrosomal spindles were shorter, more stable, had a reduced poleward microtubule flux at minus-ends, and more frequent pausing events at their plus-ends. This indicates that centrosomes regulate k-fiber dynamics both locally at minus-ends and far away at plus-ends. At the molecular level we find that the microtubule-stabilizing protein HURP is enriched on the k-fiber plus-ends in the acentrosomal spindles of cells with only one centrosome. HURP depletion rebalance k-fiber stability and dynamics in such cells, and improved spindle and cell division symmetry. Our data further indicate that HURP accumulates on k-fibers inversely proportionally to half-spindle length. We propose that centrosomes regulate k-fiber plus-ends indirectly via length-dependent accumulation of HURP. Thus by ensuring equal k-fiber length, centrosomes promote HURP symmetry, reinforcing the symmetry of the mitotic spindle and of cell division.
Identifying cortical substrates underlying the phenomenology of stereopsis and realness: A pilot fMRI study
Authors: Uji Makoto , Lingnau Angelika , Cavin Ian , Vishwanath Dhanraj 
Published: February 2019

AbstractViewing a real scene or a stereoscopic image (e.g., 3D movies) with both eyes yields a vivid subjective impression of object solidity, tangibility, immersive negative space and sense of realness; something that is not experienced when viewing single pictures of 3D scenes normally with both eyes. This phenomenology, sometimes referred to as stereopsis, is conventionally ascribed to the derivation of depth from the differences in the two eye’s images (binocular disparity). Here we report on a pilot study designed to explore if dissociable neural activity associated with the phenomenology of realness can be localised in the cortex. In order to dissociate subjective impression from disparity processing, we capitalised on the finding that the impression of realness associated with stereoscopic viewing can also be generated when viewing a single picture of a 3D scene with one eye through an aperture. Under a blocked fMRI design, subjects viewed intact and scrambled images of natural 3-D objects and scenes under three viewing conditions: (1) single pictures viewed normally with both eyes (binocular) (2) single pictures viewed with one eye through an aperture (monocular-aperture); (3) stereoscopic anaglyph images of the same scenes viewed with both eyes (binocular stereopsis). Fixed-effects GLM contrasts aimed at isolating the phenomenology of stereopsis demonstrated a selective recruitment of similar posterior parietal regions for both monocular and binocular stereopsis conditions. Our findings provide preliminary evidence that the cortical processing underlying the subjective impression of realness may be dissociable and distinct from the derivation of depth from disparity.
A voltage-based metaplasticity rule applied to the model hippocampal granule cell accounts for homeostatic heterosynaptic plasticity
Authors: Shirrafiardekani Azam , Benuskova Lubica , Frauendiener Jörg 
Published: February 2019

AbstractLong-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacies are involved in establishment of long-term memories. In this process, neurons need to adjust the overall efficacy of their synapses by using mechanisms of homeostatic plasticity to balance their activity and control their firing rate. For instance, in the dentate granule cell in vivo, induction of homosynaptic LTP in the tetanized medial perforant path is accompanied by heterosynaptic LTD in the non-tetanized lateral perforant path. We used the compartmental model of this cell to test the following hypotheses: 1. Using plasticity and metaplasticity rules both based on postsynaptic voltage we can reproduce homosynaptic LTP and concurrent heterosynaptic LTD, provided there is an ongoing noisy spontaneous activity; 2. Frequency of an ongoing noisy spontaneous activity along the lateral path determines the magnitude of heterosynaptic LTD. In experiments where procaine was used to block the lateral spontaneous activity, no heterosynaptic LTD occurred. However, when the procaine was washed out and a second tetanization was applied to the medial path, no heterosynaptic LTD could have been induced neither. Our simulations predict that the reduced frequency of spontaneous activity in the lateral perforant path can account for this lasting absence of heterosynaptic LTD.
Structural and biochemical studies of an NB-ARC domain from a plant NLR immune receptor
Authors: Steele John FC , Hughes Richard K , Banfield Mark J 
Published: February 2019

AbstractPlant NLRs are modular immune receptors that trigger rapid cell death in response to attempted infection by pathogens. A highly conservednucleotide-binding domain shared withAPAF-1, variousR-proteins andCED-4 (NB-ARC domain) is proposed to act as a molecular switch, cycling between ADP (repressed) and ATP (active) bound forms. Studies of plant NLR NB-ARC domains have revealed functional similarities to mammalian homologues, and provided insight into potential mechanisms of regulation. However, further advances have been limited by difficulties in obtaining sufficient yields of protein suitable for structural and biochemical techniques. From protein expression screens inEscherichia coliandSf9insect cells, we defined suitable conditions to produce the NB-ARC domain from the tomato NLR NRC1. Biophysical analyses of this domain showed it is a folded, soluble protein. Structural studies revealed the NRC1 NB-ARC domain had co-purified with ADP, and confirmed predicted structural similarities between plant NLR NB-ARC domains and their mammalian homologues.
Is testosterone responsible for athletic success in female athletes?
Authors: Ahmetov Ildus I. , Roos Thomas R. , Stepanova Albina A. , Biktagirova Elnara M. , Semenova Ekaterina A. , Shchuplova Irina S. , Bets Larisa V. 
Published: February 2019

AbstractThe aim of this study is to determine the interrelationship between the resting serum testosterone (T) levels (an inherited trait) of female athletes from different types of sporting events and their athletic success. The study involves 599 Russian international-level female athletes (95 highly elite, 190 elite, and 314 sub-elite) and 298 age-matched female controls. All subjects were age 16-35 years old and to the best of our knowledge have always tested negative for performance enhancing substances. The athlete cohort was stratified into four groups according to event duration, distance, and type of activity: 1) endurance athletes, 2) athletes with mixed activity, 3) speed/strength athletes, and 4) sprinters. Athletic success was measured by determining the level of achievement of each athlete. The mean (SD) T levels of athletes and controls were 1.65 (0.87) and 1.76 (0.6) nmol/L (P=0.057) with ranges of 0.08-5.80 and 0.38-2.83 nmol/L in athletes and controls, respectively. No significant differences in T levels were found between different groups of athletes. T levels were positively correlated (r=0.62, P<0.0001) with athletic success in sprinters (runners, cyclists, kayakers, speed skaters, swimmers). Moreover, none of the sub-elite sprinters had T > 1.9 nmol/L, while 50% of elite and highly elite sprinters had T > 1.9 nmol/L (95% CI: 2.562-862.34; OR=47.0; P<0.0001). We do not observe the benefits of having high T levels for success in other groups of athletes. Conversely, highly elite middle-distance (P=0.235) and mixed activity athletes (P=0.096) tended to have lower T levels than less successful athletes. Our data suggest that the measurement of the serum T levels significantly correlates with athletic success in sprinters but not other types of athletes and in the future may be useful in the prediction of sprinting ability.