bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective Inhibition of Bone Morphogenetic Protein Function by Highly Specific Llama-Derived Antibodies
Authors: Calpe Silvia , Wagner Koen , El Khattabi Mohamed , Rutten Lucy , Zimberlin Cheryl , Dolk Edward , Verrips C. Theo , Medema Jan Paul , Spits Hergen , Krishnadath Kausilia K. 
Published: September 2015

AbstractBone morphogenetic proteins (BMP) have important but distinct roles in tissue homeostasis and disease, including carcinogenesis and tumor progression. A large number of BMP inhibitors are available to study BMP function; however, as most of these antagonists are promiscuous, evaluating specific effects of individual BMPs is not feasible. Because the oncogenic role of the different BMPs varies for each neoplasm, highly selective BMP inhibitors are required. Here, we describe the generation of three types of llama-derived heavy chain variable domains (VHH) that selectively bind to either BMP4, to BMP2 and 4, or to BMP2, 4, 5, and 6. These generated VHHs have high affinity to their targets and are able to inhibit BMP signaling. Epitope binning and docking modeling have shed light into the basis for their BMP specificity. As opposed to the wide structural reach of natural inhibitors, these small molecules target the grooves and pockets of BMPs involved in receptor binding. In organoid experiments, specific inhibition of BMP4 does not affect the activation of normal stem cells. Furthermore, in vitro inhibition of cancer-derived BMP4 noncanonical signals results in an increase of chemosensitivity in a colorectal cancer cell line. Therefore, because of their high specificity and low off-target effects, these VHHs could represent a therapeutic alternative for BMP4+ malignancies. Mol Cancer Ther; 14(11); 2527–40. ©2015 AACR.
The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) Classification System
Authors: Spatz Erica S. , Curry Leslie A. , Masoudi Frederick A. , Zhou Shengfan , Strait Kelly M. , Gross Cary P. , Curtis Jeptha P. , Lansky Alexandra J. , Soares Barreto-Filho Jose Augusto , Lampropulos Julianna F. , Bueno Hector , Chaudhry Sarwat I. , D’Onofrio Gail , Safdar Basmah , Dreyer Rachel P. , Murugiah Karthik , Spertus John A. , Krumholz Harlan M. 
Published: September 2015

Background—
Current classification schemes for acute myocardial infarction (AMI) may not accommodate the breadth of clinical phenotypes in young women.

Methods and Results—
We developed a novel taxonomy among young adults (≤55 years) with AMI enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study. We first classified a subset of patients (n=600) according to the Third Universal Definition of MI using a structured abstraction tool. There was heterogeneity within type 2 AMI, and 54 patients (9%; including 51 of 412 women) were unclassified. Using an inductive approach, we iteratively grouped patients with shared clinical characteristics, with the aims of developing a more inclusive taxonomy that could distinguish unique clinical phenotypes. The final VIRGO taxonomy classified 2802 study participants as follows: class 1, plaque-mediated culprit lesion (82.5% of women; 94.9% of men); class 2, obstructive coronary artery disease with supply-demand mismatch (2a: 1.4% women; 0.9% men) and without supply-demand mismatch (2b: 2.4% women; 1.1% men); class 3, nonobstructive coronary artery disease with supply-demand mismatch (3a: 4.3% women; 0.8% men) and without supply-demand mismatch (3b: 7.0% women; 1.9% men); class 4, other identifiable mechanism (spontaneous dissection, vasospasm, embolism; 1.5% women, 0.2% men); and class 5, undetermined classification (0.8% women, 0.2% men).

Conclusions—
Approximately 1 in 8 young women with AMI is unclassified by the Universal Definition of MI. We propose a more inclusive taxonomy that could serve as a framework for understanding biological disease mechanisms, therapeutic efficacy, and prognosis in this population.
Mediators of the Age Effect in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
Authors: Voeks Jenifer H. , Howard George , Roubin Gary , Farb Richard , Heck Donald , Logan William , Longbottom Mary , Sheffet Alice , Meschia James F. , Brott Thomas G. 
Published: September 2015

Background and Purpose—
There is higher combined risk of stroke or death (S+D) at older ages with carotid stenting. We assess whether this can be attributed to patient or arterial characteristics that are in the pathway between older age and higher risk.

Methods—
Mediation analysis of selected patient (hypertension, diabetes mellitus, and dyslipidemia) and arterial characteristics assessed at the clinical sites and the core laboratory (plaque length, eccentric plaque, ulcerated plaque, percent stenosis, peak systolic velocity, and location) was performed in 1123 carotid artery stenting–treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). We assessed the association of age with these characteristics, the association of these characteristics with stroke risk, and the amount of mediation of the association of age on the combined risk of periprocedural S+D with adjustment for these factors.

Results—
Only plaque length as measured at the sites increased with age, was associated with increased S+D risk and significantly mediated the association of age on S+D risk. However, adjustment for plaque length attenuated the increased risk per 10 years of age from 1.72 (95% confidence interval, 1.26–2.37) to 1.66 (95% confidence interval, 1.20–2.29), accounting for only 8% of the increased risk.

Conclusions—
Plaque length seems to be in the pathway between older age and higher risk of S+D among carotid artery stenting–treated patients, but it mediated only 8% of the age effect excess risk of carotid artery stenting in CREST. Other factors and mechanisms underlying the age effect need to be identified as plaque length will not identify elderly patients for whom stenting is safe relative to endarterectomy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00004732.
Neural Correlates of Visual Short-term Memory Dissociate between Fragile and Working Memory Representations
Authors: Vandenbroucke Annelinde R. E. , Sligte Ilja G. , de Vries Jade G. , Cohen Michael X. , Lamme Victor A. F. 
Published: September 2015

Abstract
Evidence is accumulating that the classic two-stage model of visual STM (VSTM), comprising iconic memory (IM) and visual working memory (WM), is incomplete. A third memory stage, termed fragile VSTM (FM), seems to exist in between IM and WM [Vandenbroucke, A. R. E., Sligte, I. G., & Lamme, V. A. F. Manipulations of attention dissociate fragile visual STM from visual working memory. Neuropsychologia, 49, 1559–1568, 2011; Sligte, I. G., Scholte, H. S., & Lamme, V. A. F. Are there multiple visual STM stores? PLoS One, 3, e1699, 2008]. Although FM can be distinguished from IM using behavioral and fMRI methods, the question remains whether FM is a weak expression of WM or a separate form of memory with its own neural signature. Here, we tested whether FM and WM in humans are supported by dissociable time–frequency features of EEG recordings. Participants performed a partial-report change detection task, from which individual differences in FM and WM capacity were estimated. These individual FM and WM capacities were correlated with time–frequency characteristics of the EEG signal before and during encoding and maintenance of the memory display. FM capacity showed negative alpha correlations over peri-occipital electrodes, whereas WM capacity was positively related, suggesting increased visual processing (lower alpha) to be related to FM capacity. Furthermore, FM capacity correlated with an increase in theta power over central electrodes during preparation and processing of the memory display, whereas WM did not. In addition to a difference in visual processing characteristics, a positive relation between gamma power and FM capacity was observed during both preparation and maintenance periods of the task. On the other hand, we observed that theta–gamma coupling was negatively correlated with FM capacity, whereas it was slightly positively correlated with WM. These data show clear differences in the neural substrates of FM versus WM and suggest that FM depends more on visual processing mechanisms compared with WM. This study thus provides novel evidence for a dissociation between different stages in VSTM.
Shared and Distinct Neuroanatomic Regions Critical for Tool-related Action Production and Recognition: Evidence from 131 Left-hemisphere Stroke Patients
Authors: Tarhan Leyla Y. , Watson Christine E. , Buxbaum Laurel J. 
Published: September 2015

AbstractThe inferior frontal gyrus and inferior parietal lobe have been characterized as human homologues of the monkey “mirror neuron” system, critical for both action production (AP) and action recognition (AR). However, data from brain lesion patients with selective impairment on only one of these tasks provide evidence of neural and cognitive dissociations. We sought to clarify the relationship between AP and AR, and their critical neural substrates, by directly comparing performance of 131 chronic left-hemisphere stroke patients on both tasks—to our knowledge, the largest lesion-based experimental investigation of action cognition to date. Using voxel-based lesion-symptom mapping, we found that lesions to primary motor and somatosensory cortices and inferior parietal lobule were associated with disproportionately impaired performance on AP, whereas lesions to lateral temporo-occipital cortex were associated with a relatively rare pattern of disproportionately impaired performance on AR. In contrast, damage to posterior middle temporal gyrus was associated with impairment on both AP and AR. The distinction between lateral temporo-occipital cortex, critical for recognition, and posterior middle temporal gyrus, important for both tasks, suggests a rough gradient from modality-specific to abstract representations in posterior temporal cortex, the first lesion-based evidence for this phenomenon. Overall, the results of this large patient study help to bring closure to a long-standing debate by showing that tool-related AP and AR critically depend on both common and distinct left hemisphere neural substrates, most of which are external to putative human mirror regions.
Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions
Authors: Stamoulis Catherine , Vanderwert Ross E. , Zeanah Charles H. , Fox Nathan A. , Nelson Charles A. 
Published: September 2015

Abstract
Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1–3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross-alpha coupling was estimated in this group compared to the other two groups at 96 months, suggesting impaired suppression of alpha–theta and alpha–delta activity, which has been associated with neuropsychiatric disorders. Age at foster care placement had a significant positive modulatory effect on alpha and beta trajectories and their mutual coupling, although by 96 months these trajectories remained distinct from those of never-institutionalized children. Overall, these findings suggest that early psychosocial neglect may profoundly impact neural maturation, particularly the evolution of neural oscillations and their interactions across a broad frequency range. These differences may result in widespread deficits across multiple cognitive domains.
Food consumption pattern in the snow crab Chionoecetes opilio (Fabricius, 1788) (Decapoda, Majoidea) megalopae under laboratory conditions
Authors: Yamamoto T. , Yamada T. , Fujimoto H. , Hamasaki K. 
Published: September 2015

The food consumption pattern in megalopae of the snow crab Chionoecetes opilio (Fabricius, 1788) was investigated in the laboratory. Ten megalopae were individually cultured and given an excess of Artemia nauplii each day. All megalopae moulted into first-instar crabs 28-34 days after metamorphosis. The mean total number and total weight of Artemia consumed during the megalopal stage were 1920 individuals and 5.2 mg, respectively. Hence, the food requirement of snow crab megalopae was estimated as ∼190% of the dry body weight of the first-instar crab. Initially, the number of Artemia consumed was nearly constant or decreased only slightly but, later, Artemia consumption decreased with development days. Two-segmented regressions provided good fits to the relationship between the number of days after metamorphosis and the cumulative number of Artemia consumed by individual megalopae. The mean value of the time after metamorphosis of the breakpoint in the rate of food consumption was estimated as 69% of the stage duration, which corresponds to the intermediate of late premoult. Crab sizes (carapace width, wet and dry body weight) were not significantly dependent on the number of Artemia consumed during the entire megalopal period although a positive correlation between these variables was observed. These results provide useful information on the appropriate feeding schedule and management practice for culturing snow crab megalopae and contribute to the understanding of megalopal growth efficiency to the first-instar crab in their natural habitat.
Growth and moulting of wild-born immature snow crabs, Chionoecetes opilio (Fabricius, 1788) (Decapoda, Majoidea), in the laboratory
Authors: Yamamoto Takeo , Yamada Tatsuya , Kinoshita Takahiro , Ueda Yuji , Fujimoto Hiroshi , Yamasaki Atsushi , Hamasaki Katsuyuki 
Published: September 2015

Growth and moulting of wild-born immature snow crabs (Chionoecetes opilio (Fabricius, 1788)) were investigated by laboratory culture experiments. Crabs with 16.2-42.9 mm carapace width caught from the Sea of Japan were cultured at a temperature of their natural habitat (approximately 1°C). The growth indices (size increments at moulting in mm and in % of premoult carapace width) and intermoult period were significantly affected by premoult carapace width, but sex did not affect these variables. Furthermore, we demonstrated that premoult carapace width and days after moulting significantly affected moulting probability and we developed a moulting probability model based on these variables. From this model, the number of days of intermoult periods when moults occurred in 50% of crabs of instars VI, VII and VIII was estimated at 234, 284 and 346 days, respectively.
<em>Ramalina subfraxinea </em>Nyl. var. <em>confirmata </em>(Nyl.) N. Stevens (Ascomicete liquenizado, Ramalinaceae) en America
Authors: Marcano Antonio Morales Méndez y Vicente 
Published: September 2015

Ramalina subfraxinea Nyl. var. confirmata (Nyl.) N. Stevens is reported as new to the New World from the Venezuelan Andes. Thus far this variety was known only from Australia, New Caledonia and the Indian Ocean. It has cryptochlorophaeic acid as chemical compound. Comments about ecology and morphology are given.
Long-Term Winter Inversion Properties in a Mountain Valley of the Western United States and Implications on Air Quality
Authors: Simon Wang S.-Y. , Hipps Lawrence E. , Chung Oi-Yu , Gillies Robert R. , Martin Randal 
Published: September 2015

AbstractBecause of the geography of a narrow valley and surrounding tall mountains, Cache Valley (located in northern Utah and southern Idaho) experiences frequent shallow temperature inversions that are both intense and persistent. Such temperature inversions have resulted in the worst air quality in the nation. In this paper, the historical properties of Cache Valley’s winter inversions are examined by using two meteorological stations with a difference in elevation of approximately 100 m and a horizontal distance apart of ~4.5 km. Differences in daily maximum air temperature between two stations were used to define the frequency and intensity of inversions. Despite the lack of a long-term trend in inversion intensity from 1956 to present, the inversion frequency increased in the early 1980s and extending into the early 1990s but thereafter decreased by about 30% through 2013. Daily mean air temperatures and inversion intensity were categorized further using a mosaic plot. Of relevance was the discovery that after 1990 there was an increase in the probability of inversions during cold days and that under conditions in which the daily mean air temperature was below −15°C an inversion became a certainty. A regression model was developed to estimate the concentration of past particulate matter of aerodynamic diameter ≤ 2.5 μm (PM2.5). The model indicated past episodes of increased PM2.5 concentrations that went into decline after 1990; this was especially so in the coldest of climate conditions.
Potential Sources of Decadal Climate Variability over Southern Africa
Authors: Morioka Yushi , Engelbrecht Francois , Behera Swadhin K. 
Published: September 2015

Abstract
Potential sources of decadal climate variability over southern Africa are examined by conducting in-depth analysis of available datasets and coupled general circulation model (CGCM) experiments. The observational data in recent decades show a bidecadal variability noticeable in the southern African rainfall with its positive phase of peak during 1999/2000. It is found that the rainfall variability is related to anomalous moisture advection from the southwestern Indian Ocean, where the anomalous sea level pressure (SLP) develops. The SLP anomaly is accompanied by anomalous sea surface temperature (SST). Both SLP and SST anomalies slowly propagate eastward from the South Atlantic to the southwestern Indian Ocean. The analysis of mixed layer temperature tendency reveals that the SST anomaly in the southwestern Indian Ocean is mainly due to eastward advection of the SST anomaly by the Antarctic Circumpolar Current. The eastward propagation of SLP and SST anomalies are also confirmed in the 270-yr outputs of the CGCM control experiment. However, in a sensitivity experiment where the SST anomalies in the South Atlantic are suppressed by the model climatology, the eastward propagation of the SLP anomaly from the South Atlantic disappears. These results suggest that the local air–sea coupling in the South Atlantic may be important for the eastward propagation of the SLP anomaly from the South Atlantic to the southwestern Indian Ocean. Although remote influences from the tropical Pacific and Antarctica were widely discussed, this study provides new evidence for the potential role of local air–sea coupling in the South Atlantic for the decadal climate variability over southern Africa.
Assimilation of TRMM Multisatellite Precipitation Analysis with a Low-Resolution NCEP Global Forecast System
Authors: Lien Guo-Yuan , Miyoshi Takemasa , Kalnay Eugenia 
Published: September 2015

Abstract
Current methods of assimilation of precipitation into numerical weather prediction models are able to make the model precipitation become similar to the observed precipitation during the assimilation, but the model forecasts tend to return to their original solution after a few hours. To facilitate the precipitation assimilation, a logarithm transformation has been used in several past studies. Lien et al. proposed instead to assimilate precipitation using the local ensemble transform Kalman filter (LETKF) with a Gaussian transformation technique and succeeded in improving the model forecasts in perfect-model observing system simulation experiments (OSSEs).
In this study, the method of Lien et al. is tested within a more realistic configuration: the TRMM Multisatellite Precipitation Analysis (TMPA) data are assimilated into a low-resolution version of the NCEP Global Forecast System (GFS). With guidance from a statistical study comparing the GFS model background precipitation and the TMPA data, some modifications of the assimilation methods proposed in Lien et al. are made, including 1) applying separate Gaussian transformations to model and to observational precipitation based on their own cumulative distribution functions; 2) adopting a quality control criterion based on the correlation between the long-term model and observed precipitation data at the observation location; and 3) proposing a new method to define the transformation of zero precipitation that takes into account the zero precipitation probability in the background ensemble rather than the climatology. With these modifications, the assimilation of the TMPA precipitation data improves both the analysis and 5-day model forecasts when compared with a control experiment assimilating only rawinsonde data.
Effect of long-term olanzapine treatment on meal-induced insulin sensitization and on gastrointestinal peptides in female Sprague–Dawley rats
Authors: Hegedűs Csaba , Kovács Diána , Kiss Rita , Sári Réka , Németh József , Szilvássy Zoltán , Peitl Barna 
Published: September 2015

Meal-induced insulin sensitization (MIS), an endogenous adaptive mechanism is activated post-prandially. Reduced MIS leads to diabetes, but its activation improves insulin sensitivity. MIS is preserved to single olanzapine administration, therefore we aimed to investigate the chronic effect of olanzapine on fasted-state insulin sensitivity and on MIS in female Sprague–Dawley rats. Daily food and water intake, stool and urine production and body weight were determined. The MIS was characterized by a rapid insulin sensitivity test. Fasting hepatic and peripheral insulin sensitivity were determined by a hyperinsulinaemic euglycaemic glucose clamping supplemented with radiotracer technique. Fasted and post-prandial blood samples were obtained for plasma insulin, leptin, ghrelin, amylin, GLP-1, GIP, PYY and PP determination. Adiposity was characterized by weighing intra-abdominal and inguinal fat pads. Olanzapine caused hepatic insulin resistance and a reduced metabolic clearance rate of insulin, but the MIS retained its function. Body weight and adiposity were enhanced, but olanzapine failed to increase food intake. Fasting insulin and leptin were elevated and the post-prandial reduction in ghrelin level was inhibited by olanzapine. The MIS remained functionally intact after long-term olanzapine treatment. Altered insulin, leptin and ghrelin levels indicate olanzapine-induced metabolic derangements. Pharmacological activation of MIS could potentially be exploited to treat or prevent olanzapine-induced insulin resistance.