bluuebunny/crossref_metadata_2025 huggingface dataset:
Solvation of barium atoms and singly charged cations in acetonitrile clusters
Authors: Taccone Martín I. , Berdakin Matías , Baptista Leonardo , Pino Gustavo A. , Rossa Maximiliano
Published: September 2018

The size distributions of neutral and cationic Bax(CH3CN)n (x = 0, +1; n ≤ 7) clusters, as produced by a standard laser vaporization-supersonic expansion pick-up source, were determined from molecular beam experiments. The size distribution for cations is in the range of n = 1-7, whereas only the n = 1 complex is observed for neutral clusters, and these two features are unaffected by the variables controlling the performance of the cluster source. The distinct behavior is compatible with the expected charge-dipole interactions in the ionic species, which are stronger than the dipole induced-dipole interactions at play in neutral clusters, and it is corroborated by the relative magnitude of the theoretical successive binding energies (SBEs) for the lowest-lying isomers of cationic and neutral clusters with n = 1-5, as computed at the density functional theory level. The theoretical results also allow for the rationalization of the bimodal Ba+(CH3CN)1-7 size distribution, featuring an apparent minimum at n = 3, in terms of chiefly 6s-5d σ hybridization of the Ba+ ions, which ultimately leads to a relatively small third SBE for the Ba+(CH3CN)3 complex, as compared to those for n = 1, 2, and 4. Additional Born-Oppenheimer molecular dynamics simulations on the Ba+(CH3CN)2-4 clusters suggest that all of the ligands are coordinated to the Ba+ ion and prevent considering completion of the first solvent shell as responsible for the bimodal size distribution.
Evolutions of packing properties of perfect cylinders under densification and crystallization
Authors: Liu Lufeng , Yuan Ye , Deng Wei , Li Shuixiang
Published: September 2018

Cylindrical particles are ubiquitous in nature and industry, and a cylinder is a representative shape of rod-like particles. However, the disordered packing results of cylinders in previous studies are quite inconsistent with each other. In this work, we obtain the MRJ (maximally random jammed) packings and the MDRPs (maximally dense random packings) of perfect cylinders with the aspect ratio (height/diameter) 0.2 ≤ w ≤ 6.0 using the ASC (adaptive shrinking cell) algorithm and the IMC (inverse Monte Carlo) method, respectively. The optimal aspect ratio corresponding to the maximal packing density is w = 0.9 in the MRJ state, while the value is w = 1.2 in the MDRP state. Then we investigate the evolutions of packing properties of perfect cylinders under densification and crystallization. We compare the different final packing states generated via the two methods with different compression rates and order constraints. In the densification procedure, we generate jammed and random packings of cylinders with various compression rates via the ASC and IMC method, respectively. When decreasing the compression rate, we find that the packing density increases but the optimal w remains the same in both methods. In the crystallization procedure, the order constraint in the IMC method is gradually released which means the degree of order in the packings is allowed to increase, and we find that the optimal w shifts from 1.2 to 0.9 while the packing density increases as well. Meanwhile, the random packings evolve into the jammed packings in the crystallization procedure which reflects the competition mechanism between the randomness and jamming. These results also indicate that the optimal w is solely related to the degree of order in the cylinder packings but not determined by the protocol or packing density. Furthermore, a uniform shape elongation effect on the random-packing densities of various shaped particles is found via a new proposed definition of the scaled aspect ratio. Finally, a rough linear relationship between the mean and standard deviation of the reduced Voronoi cell volumes is obtained only for the random packings. Our findings should lead to a better understanding toward the jammed and random packings and are helpful in guiding the granular material design.
Fast spontaneous emission and high Förster resonance energy transfer rate in hybrid organic/inorganic plasmonic nanostructures
Authors: Asgar Hassnain , Jacob Liyan , Hoang Thang B.
Published: September 2018

We report an experimental study of the plasmon-assisted spontaneous emission and the Förster resonance energy transfer between organic molecules and semiconductor colloidal quantum dots. The localized plasmonic field in the nanogap between a gold nano-popcorn's tips and a 5-nm separated gold film supports high photonic density of states and provides pathways for the light-matter interaction mechanisms. We demonstrate that, besides the total enhanced decay rate up to 66 times for quantum dots and molecules, the Förster resonance energy transfer efficiency and rate constant are simultaneously modified. While the energy transfer efficiency is reduced from 84% to 35% due to the non-radiative quenching effect and fast donor decay rate, the energy transfer rate constant is significantly increased from 4 to 20 ns−1. Our results have quantitatively elucidated decay mechanisms that are important toward understanding and controlling of the light-matter interaction at the nanoscale.
Artificial intelligence characterizes rotational spectroscopy
Authors: Agner Mary Alexandra
Published: September 2018

Artificial neural networks quickly and accurately identify and characterize rotational spectra.
Parp3 promotes long-range end joining in murine cells
Authors: Layer Jacob V. , Cleary J. Patrick , Brown Alexander J. , Stevenson Kristen E. , Morrow Sara N. , Van Scoyk Alexandria , Blasco Rafael B. , Karaca Elif , Meng Fei-Long , Frock Richard L. , Tivey Trevor , Kim Sunhee , Fuchs Hailey , Chiarle Roberto , Alt Frederick W. , Roberts Steven A. , Weinstock David M. , Day Tovah A.
Published: September 2018

Significance

Chromosomal rearrangements are early and essential events in the formation of many tumors. Two distinct end-joining pathways, classic and alternative nonhomologous end joining, can mediate rearrangement formation. Previous studies have shown that genetic factors mediating rearrangements differ significantly between mouse and human cells. Here we show that poly(ADP)ribose polymerase 3 (Parp3) uniquely promotes chromosomal rearrangements in both species. Using next-generation sequencing of rearrangement junctions, we investigated the mechanistic contribution of Parp3 and a closely related enzyme, Parp1, that is also known to promote rearrangements in murine cells. We find differences in the phenotypes of rearrangements in cells lacking Parp3, Parp1, or both, suggesting that these enzymes promote rearrangements through distinct mechanisms and providing insight into this essential mechanism of tumorigenesis.
Highlighting the goals for Parkinson’s care: commentary on NICE Guidelines for Parkinson’s in Adults (NG71)
Authors: Brock Peter , Fisher James M , Hand Annette , Walker Richard W
Published: September 2018

Parkinson’s disease is a chronic multi-system disease that can cause motor and non-motor symptoms, cognitive changes and variably effective medications. Optimal management of the condition requires a multi-disciplinary team of healthcare professionals to work closely with the patient and their carers. The National Institute for Health and Care Excellence published updated guidelines on managing Parkinson’s disease in adults in 2017. Here we discuss the implications of this guidance to current healthcare professionals involved in the care of people with Parkinson’s disease.

The guidance highlights the importance of clear communication with people with Parkinson’s disease. We discuss examples of this, including providing a point of contact with specialist services for people with Parkinson’s disease and ensuring information about the risks of impulse control disorders are given to people on dopaminergic therapy. The breadth of services required by people with Parkinson’s disease is also described, including the need for access to physiotherapy, occupational therapy and speech and language therapy as well as treatment monitoring services for Clozapine. In addition, we emphasise the continued importance of ensuring people with Parkinson’s disease receive their medications on time when in hospital or a care home.
Combining count- and length-based z-scores leads to improved predictions in non-invasive prenatal testing
Authors: Budis Jaroslav , Gazdarica Juraj , Radvanszky Jan , Szucs Gabor , Kucharik Marcel , Strieskova Lucia , Gazdaricova Iveta , Harsanyova Maria , Duris Frantisek , Minarik Gabriel , Sekelska Martina , Nagy Balint , Turna Jan , Szemes Tomas
Published: September 2018

Motivation

Non-invasive prenatal testing or NIPT is currently among the top researched topic in obstetric care. While the performance of the current state-of-the-art NIPT solutions achieve high sensitivity and specificity, they still struggle with a considerable number of samples that cannot be concluded with certainty. Such uninformative results are often subject to repeated blood sampling and re-analysis, usually after two weeks, and this period may cause a stress to the future mothers as well as increase the overall cost of the test.

Results

We propose a supplementary method to traditional z-scores to reduce the number of such uninformative calls. The method is based on a novel analysis of the length profile of circulating cell free DNA which compares the change in such profiles when random-based and length-based elimination of some fragments is performed. The proposed method is not as accurate as the standard z-score; however, our results suggest that combination of these two independent methods correctly resolves a substantial portion of healthy samples with an uninformative result. Additionally, we discuss how the proposed method can be used to identify maternal aberrations, thus reducing the risk of false positive and false negative calls.

Availability and implementation

The open-source code of the proposed methods, together with test data, is freely available for non-commercial users at github web page https://github.com/jbudis/lambda.

Supplementary information

Supplementary materials are available at Bioinformatics online.
Trajectories and Milestones of Cortical and Subcortical Development of the Marmoset Brain From Infancy to Adulthood
Authors: Sawiak S J , Shiba Y , Oikonomidis L , Windle C P , Santangelo A M , Grydeland H , Cockcroft G , Bullmore E T , Roberts A C
Published: September 2018

With increasing attention on the developmental causes of neuropsychiatric disorders, appropriate animal models are crucial to identifying causes and assessing potential interventions. The common marmoset is an ideal model as it has sophisticated social/emotional behavior, reaching adulthood within 2 years of birth. Magnetic resonance imaging was used in an accelerated longitudinal cohort (n = 41; aged 3–27 months; scanned 2–7 times over 2 years). Splines were used to model nonlinear trajectories of grey matter volume development in 53 cortical areas and 16 subcortical nuclei. Generally, volumes increased before puberty, peaked, and declined into adulthood. We identified 3 milestones of grey matter development: I) age at peak volume; II) age at onset of volume decline; and III) age at maximum rate of volume decline. These milestones differentiated growth trajectories of primary sensory/motor cortical areas from those of association cortex but also revealed distinct trajectories between association cortices. Cluster analysis of trajectories showed that prefrontal cortex was the most heterogenous of association regions, comprising areas with distinct milestones and developmental trajectories. These results highlight the potential of high-field structural MRI to define the dynamics of primate brain development and importantly to identify when specific prefrontal circuits may be most vulnerable to environmental impact.
Modeling Cornelia de Lange syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation
Authors: Bottai Daniele , Spreafico Marco , Pistocchi Anna , Fazio Grazia , Adami Raffaella , Grazioli Paolo , Canu Adriana , Bragato Cinzia , Rigamonti Silvia , Parodi Chiara , Cazzaniga Gianni , Biondi Andrea , Cotelli Franco , Selicorni Angelo , Massa Valentina
Published: September 2018

Cornelia de Lange syndrome (CdLS), which is reported to affect ∼1 in 10 000 to 30 000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition. CdLS can result from mutations in at least five genes: nipped-B-like protein, structural maintenance of chromosomes 1A, structural maintenance of chromosomes 3, RAD21 cohesin complex component and histone deacetylase 8 (HDAC8). It is believed that mutations in these genes cause CdLS by impairing the function of the cohesin complex (to which all the aforementioned genes contribute to the structure or function), disrupting gene regulation during critical stages of early development. Since intellectual disorder might result from alterations in neural development, in this work, we studied the role of Hdac8 gene in mouse neural stem cells (NSCs) and in vertebrate (Danio rerio) brain development by knockdown and chemical inhibition experiments. Underlying features of Hdac8 deficiency is an increased cell death in the developing neural tissues, either in mouse NSCs or in zebrafish embryos.
Guatemala City youth: an analysis of health indicators through the lens of a clinical registry
Authors: Golub Sarah A , Maza Reyes Juan Carlos , Stamoulis Catherine , Leal Pensabene Alejandra , Tijerino Cordón Pablo Alejandro , Calgua Erwin , Hassan Areej
Published: September 2018

Background

Despite the inclusion of adolescent health in recent global frameworks, limited data exist on health indicators in low-income countries. Our objective was to identify socioeconomic measures, risk behaviors and health indicators of young people in Guatemala.

Methods

We conducted a secondary data analysis of the Pan American Health Organization’s Sistema Informático del Adolescente of 2831 participants ages 10–24 y from 2008 to 2014. We examined frequencies for a core set of items, and generalized regression models assessed correlations between age, sex and ethnicity with health outcomes of interest.

Results

Fewer than 17% of participants reported a history of chronic illness (16.6%) and severe psychological problems (16.8%). While 66.1% of participants’ mothers and 36.6% of fathers reported job instability, far fewer families had housing instability (1.9% with no electricity, 6.3% with no running water). Fewer than one-third (29.1%) were sexually active and the majority (76.0%) routinely used condoms. About one-quarter (22.6%) reported abnormal mood. Indigenous participants were significantly more likely to have experienced psychological problems (odds ratio [OR] 1.75 [confidence interval {CI} 1.65–1.86]) and violence (OR 1.34 [CI 1.27–1.42]) compared with whites.

Conclusions

The prevalence of risk behaviors and mental health concerns is low compared with other sources of national and regional data. Further work is needed to examine the benefits and limitations of this system in order to improve health surveillance.
Outcomes of Retreatment for Intracranial Aneurysms — A Meta-Analysis
Authors: Muskens Ivo S , Hertgers Omar , Lycklama à Nijeholt Geert J , Broekman Marike L D , Moojen Wouter A
Published: September 2018

BACKGROUND

Long-term results from the International Subarachnoid Hemorrhage Trial (ISAT) and Barrow Ruptured Aneurysm Trial (BRAT) indicate considerably higher retreatment rates for aneurysms treated with coiling compared to clipping, but do not report the outcome of retreatment.

OBJECTIVE

To evaluate retreatment related outcomes.

METHODS

A meta-analysis in accordance with PRISMA guidelines was conducted using Medline search engines PubMed and EMBASE to identify articles describing outcomes after retreatment for intracranial aneurysms. Pooled prevalence rates for complete occlusion rate and mortality were calculated. Outcomes of different treatment and retreatment combinations were not compared because of indication bias.

RESULTS

Twenty-five articles that met the inclusion criteria were included in the meta-analysis. Surgery after coiling had a pooled complete occlusion rate of 91.2% (95% confidence interval [CI]: 87.0-94.1) and a pooled mortality rate of 5.6% (95% CI: 3.7-8.3). Coiling after coiling had a pooled complete occlusion rate of 51.3% (95% CI: 22.1-78.0) and a pooled mortality rate of 0.8% (95% CI: 0.15-3.7). Surgery after surgery did not provide a pooled estimate for complete occlusion as only one study was identified but had a pooled mortality rate of 5.9% (95% CI: 3.1-11.2). Coiling after surgery had a pooled complete occlusion rate of 56.1% (95% CI: 11.4-92.7) and a pooled mortality rate of 9.3% (95% CI: 4.1-19.9). All pooled incidence rates were produced using random-effect models.

CONCLUSION

Surgical retreatment was associated with a high complete occlusion rate but considerable mortality. Conversely, endovascular retreatment was associated with low mortality but also a low complete occlusion rate.
ESTIMATION OF ORGAN DOSES AND EFFECTIVE DOSES BASED ON IN-PHANTOM DOSIMETRY FOR INFANT DIAGNOSTIC CARDIAC CATHETERISATIONS WITH NOVEL X-RAY IMAGING TECHNOLOGY
Authors: Kawasaki Toshio , Sakakubo Masami , Ito Kanako
Published: September 2018

The present study evaluated the organ and effective doses in infant diagnostic cardiac catheterisation performed using a modern x-ray imaging unit by in-phantom dosimetry. In addition, conversion factors from dose–area product (DAP) to effective dose were determined. The organ and effective doses in 1-year old during diagnostic cardiac catheterisations were measured using radiophotoluminescence glass dosemeters implanted into an infant anthropomorphic phantom. The mean effective doses, evaluated according to the International Commission on Radiologic Protection Publication 103, were 4.0 mSv (range: 1.5–8.7 mSv). The conversion factors from DAP to effective dose were 2 and 3.5 mSv (Gy cm2)−1 for posteroanterior and lateral fluoroscopy, respectively, and 1.8 and 3.3 mSv (Gy cm2)−1 for posteroanterior and lateral cineangiography, respectively. The dose data and conversion factors evaluated in the present study may be useful for estimating radiation exposure in infants during diagnostic cardiac catheterisation.
NATURAL RADIOACTIVITY AND EVALUATION OF RADIATION HAZARDS IN SOILS FROM GRANITOIDE-GRANITE GEOLOGICAL FORMATION IN CUBA
Authors: Alonso-Hernández C M , Toledo-Sibello A L , Guillén-Arruebarrena A , Sibello-Hernández R , Morera-Gómez Y , Cartas-Águila H A
Published: September 2018

The natural radioactivity and the associated radiation hazards of soils from the Cumanayagua Granitoide-Granitic massif in the central south of Cuba have been studied. Mass activities of the natural radionuclides 238U, 232Th and 40K varied in the ranges 10.4–33, 4.6–21.7 and 381–1201 Bq kg−1, respectively. The radium equivalent activity (91.4 ± 22.1 Bq kg−1), absorbed dose rate (45.6 ± 11.1 nGy h−1), annual effective dose rate (56.1 ± 13.7 μSv y−1) and the external hazard index (0.25 ± 0.06) have been calculated and compared with the internationally approved values. According to these results, the area can be regarded as an area with normal natural background radiation and may not pose radiological risks to the inhabitants owing to harmful effects of ionizing radiation from the natural radionuclides in soils. This study provides background radioactivity concentrations in Cumanayagua Granitoide area and generate a baseline data for radiological mapping of Cuba in the future.
uORF-Tools – Workflow for the determination of translation-regulatory upstream open reading frames
Authors: Scholz Anica , Eggenhofer Florian , Gelhausen Rick , Grüning Björn , Zarnack Kathi , Brüne Bernhard , Backofen Rolf , Schmid Tobias
Published: September 2018

Ribosome profiling (ribo-seq) provides a means to analyze active translation by determining ribosome occupancy in a transcriptome-wide manner. The vast majority of ribosome protected fragments (RPFs) resides within the protein-coding sequence of mRNAs. However, commonly reads are also found within the transcript leader sequence (TLS) (aka 5’ untranslated region) preceding the main open reading frame (ORF), indicating the translation of regulatory upstream ORFs (uORFs). Here, we present a workflow for the identification of translation-regulatory uORFs. Specifically, uORF-Tools identifies uORFs within a given dataset and generates a uORF annotation file. In addition, a comprehensive human uORF annotation file, based on 35 ribo-seq files, is provided, which can serve as an alternative input file for the workflow. To assess the translation-regulatory activity of the uORFs, stimulus-induced changes in the ratio of the RPFs residing in the main ORFs relative to those found in the associated uORFs are determined. The resulting output file allows for the easy identification of candidate uORFs, which have translation-inhibitory effects on their associated main ORFs. uORF-Tools is available as a free and open Snakemake workflow at https://github.com/Biochemistry1-FFM/uORF-Tools. It is easily installed and all necessary tools are provided in a version-controlled manner, which also ensures lasting usability. uORF-Tools is designed for intuitive use and requires only limited computing times and resources.
FirstSV: Fast and Accurate Approach of Structural Variations Detection for Short DNA fragments
Authors: Shen Jia , Zuo Qiyang , Wang Rongliang , Li Xiang , Tang Yuanhua
Published: September 2018

Structural variations caused by gene fusion represent a major class of somatically acquired variations in human malignancies, and include deletions, inversions, and translocations. Short fragmented reads are the main source of data from 2nd-generation sequencing, and detecting structural variations from this type of data is different from that of 1st-generation sequencing, where the read length is much longer. Current detection methods are low in specificity and are inefficient. We developed a hybrid algorithm, FirstSV, to meet the clinical demand for fast and accurate structural variation detection. Its main features include cluster analysis, realignment, and local assembly. FirstSV was validated with simulated data, with data from real patient samples, with data from standard testing samples, and with downloaded public data sets. FirstSV outperforms public-available methods in terms of sensitivity, precision, and operational efficiency. FirstSV is freely available at https://github.com/shenjia1/FirstSV.
Uncovering a role for the dorsal hippocampal commissure in episodic memory
Authors: Postans M , Parker GD , Lundell H , Ptito M , Hamandi K , Gray WP , Aggleton JP , Dyrby TB , Jones DK , Winter M
Published: September 2018

The dorsal hippocampal commissure (DHC) is a white matter tract that provides inter-hemispheric connections between temporal lobe brain regions. Despite the importance of these regions for learning and memory, there is scant evidence of a role for the DHC in successful memory performance. We used diffusion-weighted MRI (DW-MRI) and white matter tractography to reconstruct the DHC across both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings demonstrate close consistency between the known anatomy and tract reconstructions of the DHC. Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in nonhuman primates. Finally, we derived Diffusion Tensor MRI (DT-MRI) metrics from the DHC in a large sample of human subjects to investigate whether inter-individual variation in DHC microstructure is predictive of memory performance. The mean diffusivity of the DHC was correlated with performance in a standardised episodic memory task; an effect that was not reproduced in a comparison commissure tract – the anterior commissure. These findings highlight a role for the DHC in episodic memory, and our tract reconstruction approach has the potential to generate further novel insights into the role of this previously understudied white matter tract in both health and disease.
Genome based meta-QTL analysis of grain weight in tetraploid wheat identifies rare alleles ofGRF4associated with larger grains
Authors: Avni Raz , Oren Leah , Shabtai Gai , Assili Siwar , Pozniak Curtis , Hale Iago , Ben-David Roi , Peleg Zvi , Distelfeld Assaf
Published: September 2018

The domestication and subsequent genetic improvement of wheat led to the development of large-seeded cultivated wheat species relative to their smaller-seeded wild progenitors. While increased grain weight (GW) continues to be an important goal of many wheat breeding programs, few genes underlying this trait have been identified despite an abundance of studies reporting quantitative trait loci (QTLs) for GW. Here we perform a QTL analysis for GW using a population of recombinant inbred lines (RILs) derived from the cross between wild emmer wheat accession ‘Zavitan’ and durum wheat variety ‘Svevo’. Identified QTLs in this population were anchored to the recent Zavitan reference genome, along with previously published QTLs for GW in tetraploid wheat. This genome-based, meta-QTL analysis enabled the identification of a locus on chromosome 6A whose introgression from wild wheat positively affects GW. The locus was validated using an introgression line carrying the 6A GW QTL region from Zavitan in a Svevo background, resulting in >8% increase in GW compared to Svevo. Using the reference sequence for the 6A QTL region, we identified a wheat ortholog to OsGRF4, a rice gene previously associated with GW. The coding sequence of this gene (TtGRF4-A) contains four SNPs between Zavitan and Svevo, one of which reveals the Zavitan allele to be rare in a core collection of wild emmer and completely absent from the domesticated emmer genepool. Similarly, another wild emmer accession (G18-16) was found to carry a rare allele ofTtGRF4-Athat also positively affects GW and is characterized by a unique SNP absent from the entire core collection. These results exemplify the rich genetic diversity of wild wheat, positTtGRF4-Aas a candidate gene underlying the 6A GW QTL, and suggest that the natural Zavitan and G18-16 alleles ofTtGRF4-Ahave potential to increase wheat yields in breeding programs.
HSCs Contribute Actively to Native Multilineage Hematopoiesis but With Reduced Differentiation Capacity Upon Aging
Authors: Säwén Petter , Eldeeb Mohamed , Erlandsson Eva , Kristiansen Trine A , Laterza Cecilia , Kokaia Zaal , Karlsson Göran , Yuan Joan , Soneji Shamit , Mandal Pankaj K. , Rossi Derrick J , Bryder David
Published: September 2018

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. It is well established that adult hematopoietic stem cells (HSCs) are active contributors to these processes after transplantation, yet their role in native hematopoiesis has recently been called into question. Here, we use inducible lineage tracing from genetically marked adult HSCs to explore their roles in the steady state. We show that adult HSCs contribute robustly to all lineages via intermediate progenitor cells, but with neglible production of hematopoietic cells with a known fetal origin. We further reveal that the timing for regeneration of distinct blood lineages varies substantially. Finally, HSC contribution to multilineage hematopoiesis in aged animals declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for a reduced differentiation capacity with age.
Cortical Mechanisms for Reaches Versus Saccades: Progression of Effector-Specificity Through Target Memory to Movement Planning and Execution
Authors: Cappadocia David C. , Monaco Simona , Chen Ying , Crawford J. Douglas
Published: September 2018

Effector-specific cortical mechanisms can be difficult to establish using fMRI, in part because low time resolution might temporally conflate different signals related to target representation, motor planning, and motor execution. Here, we used an event-related fMRI protocol and a cue-separation paradigm to temporally separate these three major sensorimotor stages for saccades vs. reaches. In each trial, subjects (N=12) 1) briefly viewed a target 4-7° left or right of midline fixation on a touchscreen, followed by an 8 second delay (effector-independent target memory phase), 2) were instructed by an auditory cue to perform a reach or a saccade, followed by a second delay of 8 seconds (effector-specific planning phase), and finally 3) were prompted to move by reaching-to-touch or performing a saccade towards the remembered target (effector-specific execution phase). Our analysis of saccade and reach activation (vs. a non-spatial control task) revealed modest effector-agnostic target memory activity (left AG, bilateral mIPS) followed by independent effector parietofrontal sites and time courses during the motor components of the task, specifically: more medial (pIPS, mIPS, M1, and PMd) activity during both reach planning and execution, and more lateral (mIPS, AG, and FEF) activity only during saccade execution. These motor activations were bilateral, with a left (contralateral) preference for reach. A conjunction analysis revealed that left mIPS and right AG, PCu, SPOC, FEF/PMv and LOTC showed activation for both saccades and reaches. Overall, effector-preference contrasts (reach vs. saccade) revealed significantly more parietofrontal activation for reaches than saccades during both planning and execution, with the exception of FEF. Cross-correlation of reach, saccade, and reach-saccade activation through time revealed correlated activation both within and across effectors in each hemisphere, but with a tendency toward higher correlations in the right hemisphere, especially between the eye and hand. These results demonstrate substantially independent but temporally correlated cortical networks for human eye, hand, and eye-hand control, that follow explicit spatiotemporal rules for effector-specific timing, medial-lateral distribution, and hemispheric lateralization.
Cross-decoding reveals shared brain activity patterns between saccadic eye-movements and semantic processing of implicitly spatial words
Authors: Ostarek Markus , Paridon Jeroen van , Huettig Falk
Published: September 2018

Processing words with referents that are typically observed up or down in space (up/down words) influences the subsequent identification of visual targets in congruent locations. Eye-tracking studies have shown that up/down word comprehension shortens launch times of subsequent saccades to congruent locations and modulates concurrent saccade trajectories. This can be explained by a task-dependent interaction of semantic processing and oculomotor programs or by a direct recruitment of direction-specific processes in oculomotor and spatial systems as part of semantic processing. To test the latter possibility, we conducted a functional magnetic resonance imaging experiment and used multi-voxel pattern analysis to assess 1) whether the typical location of word referents can be decoded from the fronto-parietal spatial network and 2) whether activity patterns are shared between up/down words and up/down saccadic eye movements. In line with these hypotheses, significant decoding of up vs. down words and cross-decoding between up/down saccades and up/down words were observed in the frontal eye field region in the superior frontal sulcus and the inferior parietal lobule. Beyond these spatial attention areas, typical location of word referents could be decoded from a set of occipital, temporal, and frontal areas, indicating that interactions between high-level regions typically implicated with lexical-semantic processing and spatial/oculomotor regions constitute the neural basis for access to spatial aspects of word meanings.
A synthetic biology platform for the reconstitution and mechanistic dissection of LINC complex assembly
Authors: Majumder Sagardip , Willey Patrick T. , DeNies Maxwell S. , Liu Allen P. , Luxton G.W. Gant
Published: September 2018

The linker of nucleoskeleton and cytoskeleton (LINC) is a conserved nuclear envelope-spanning molecular bridge that is responsible for the mechanical integration of the nucleus with the cytoskeleton. LINC complexes are formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Despite recent structural insights, our mechanistic understanding of LINC complex assembly remains limited by the lack of an experimental system for its in vitro reconstitution and manipulation. Here, we describe artificial nuclear membranes (ANMs) as a synthetic biology platform based on mammalian cell-free expression for the rapid reconstitution of SUN proteins in supported lipid bilayers. We demonstrate that SUN1 and SUN2 are oriented in ANMs with solvent-exposed C-terminal KASH-binding SUN domains. We also find that SUN2 possesses a single transmembrane domain, while SUN1 possesses three. Finally, SUN protein-containing ANMs bind synthetic KASH peptides, thereby reconstituting the LINC complex core. This work represents the first in vitro reconstitution of KASH-binding SUN proteins in supported lipid bilayers using cell-free expression, which will be invaluable for testing proposed models of LINC complex assembly and its regulation.
The Plant PTM Viewer, a central resource exploring plant protein modifications. From site-seeing to protein function
Authors: Willems Patrick , Horne Alison , Goormachtig Sofie , Smet Ive De , Botzki Alexander , Breusegem Frank Van , Gevaert Kris
Published: September 2018

Posttranslational modifications (PTMs) of proteins are central in any kind of cellular signaling. Modern mass spectrometry technologies enable comprehensive identification and quantification of various PTMs. Given the increased number and types of mapped protein modifications, a database is necessary that simultaneouly integrates and compares site-specific information for different PTMs, especially in plants for which the available PTM data are poorly catalogued. Here, we present the Plant PTM Viewer (http://www.psb.ugent.be/PlantPTMViewer), an integrative PTM resource that comprises approximately 200,000 PTM sites for 17 types of protein modifications in plant proteins from five different species. The Plant PTM Viewer provides the user with a protein sequence overview in which the experimentally evidenced PTMs are highlighted together with functional protein domains or active site residues. The PTM sequence search tool can query PTM combinations in specific protein sequences, whereas the PTM BLAST tool searches for modified protein sequences to detect conserved PTMs in homologous sequences. Taken together, these tools facilitate to assume the role and potential interplay of PTMs in specific proteins or within a broader systems biology context. The Plant PTM Viewer is an open repository that allows submission of mass spectrometry-based PTM data to remain at pace with future PTM plant studies.
Laboratory surrogate markers of residual HIV replication among distinct groups of individuals under antiretroviral therapy
Authors: Giron L.B. , Tenore S.B. , Janini L.M. , Sucupira M.C. , Diaz R.S.
Published: September 2018

Background

Residual HIV-1 replication among individuals under antiretroviral therapy (ART) relates to HIV micro-inflammation.

Objectives

To determine levels of residual HIV replication markers among distinct subgroups of antiretroviral-treated individuals.

Methods

116 patients were distributed into 5 treatment groups: first-line suppressive ART with non-nucleoside reverse-transcriptase inhibitor (NNRTI) (n=26), first-line suppressive ART with boosted protease inhibitors (PI-r) (n=25), salvage therapy using PI-r (n=27), salvage therapy with PI-r and raltegravir (n=22) and virologic failure (n=16). Episomal and total DNA quantitation was evaluated. ELISA was used for HIV antibody and LPS quantitation.

Results

Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, being higher among individuals experiencing virologic failure (p=0.04). HIV proviral load was higher among patients with detectable episomal DNA (p=0.01). Individuals receiving initial PI-r treatment presented lower HIV antibodies (p=0.027) and LPS (p=0.029) than individuals receiving NNRTI. There was a negative correlation between episomal DNA quantitation and suppressive ART duration (p=0.04), CD4+ T-cell count (p=0.08), and CD8+ T-cell count (p=0.07).

Conclusions

Residual HIV replication has been inferred among individuals under suppressive ART according to episomal DNA detection. Residual replication may decrease with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The relationship between episomal DNA and total DNA suggests a replenishment of the proviral reservoir with impacts on HIV persistence. Lower antibody and LPS levels among patients with initial PI-r ART suggest these regimens may more effectively suppress HIV with higher capacity to decrease the HIV antigenic component.
Endothelial cells form transient Notch-dependent NO-containing cystic structures during zebrafish cerebrovascular development
Authors: Kugler E. , Chhabria K. , Daetwyler S. , Huisken J. , Plant K. , Savage A.M. , Wilkinson R.N. , Armitage P.A. , Chico T.J.A.
Published: September 2018

Endothelial cell behaviour during blood vessel formation is highly complex and dynamic. Transgenic zebrafish have provided many new insights into these processes, due to their ability to provide detailed in vivo imaging.

We here report a previously undescribed endothelial cell behaviour during zebrafish embryonic development. Endothelial cells of the cerebral vessels of 3-5d post fertilisation embryos extruded large membranous spherical structures. These were only found on the cerebral vessels, and did not detach from the parent vessel, instead regressing back into the endothelial cell. These structures did not communicate with the vessel lumen, exhibited periodic oscillations in size and shape, and were enriched with filamentous actin at their neck. Due to their unknown nature and spherical appearance we termed these structures kugeln (German for sphere).

Pharmacological inhibition of vascular endothelial growth factor (VEGF) signalling significantly increased kugel number while Notch inhibition significantly reduced both kugel number and diameter. Kugeln contain little cytoplasm, but are highly positive for nitric oxide (NO) reactivity, suggesting they represent a novel NO containing organelle specific to the cerebral vessels.
In vivo assay of cortical microcircuitry in frontotemporal dementia: a platform for experimental medicine studies
Authors: Shaw Alexander D , Hughes Laura E , Moran Rosalyn , Coyle-Gilchrist Ian , Rittman Tim , Rowe James B
Published: September 2018

The analysis of neural circuits can provide critical insights into the mechanisms of neurodegeneration and dementias, and offer potential quantitative biological tools to assess novel therapeutics. Here we use behavioural variant frontotemporal dementia (bvFTD) as a model disease. We demonstrate that inversion of canonical microcircuit models to non-invasive human magnetoecphalography can identify the regional- and laminar-specificity of bvFTD pathophysiology, and their parameters can accurately differentiate patients from matched healthy controls. Using such models, we show that changes in local coupling in frontotemporal dementia underlie the failure to adequately establish sensory predictions, leading to altered prediction error responses in a cortical information-processing hierarchy. Using machine learning, this model-based approach provided greater case-control classification accuracy than conventional evoked cortical responses. We suggest that this approach provides an in vivo platform for testing mechanistic hypotheses about disease progression and pharmacotherapeutics.
A transgenic mutant mouse line accompanied by the complete deletion of interleukin-33 showed insulin and leptin resistances
Authors: Watanabe Taku , Takeuchi Tomonori , Kubota Naoto , Wainai Tasuku , Kataoka Keisuke , Nakaya Toshitaka , Sugimoto Ayako , Sato Takahiro , Ohira Hiroshi , Tsujino Ichizo , Kumagai Katsuyoshi , Kubota Tetsuya , Hasegawa Chiaki , Tokuyama Kumpei , Ueki Kohjiro , Yamauchi Toshimasa , Mishina Masayoshi , Kadowaki Takashi
Published: September 2018

Interleukin (IL) −33 has been identified as a member of the IL-1 family. Members of the IL-1 family have been reported to be involved in the regulation of energy homeostasis and glucose metabolism. Homozygous transgenic mutant mice of FLP14 line, that we previously generated, unexpectedly developed mature-onset obesity and diabetes. Through genetic investigations, we found that insertion of the transgenes had resulted in complete deletion of the Il33 gene. These obese male homozygous mutant mice exhibited hyperphagia with hyperleptinemia and insulin resistance caused by increased hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle. As a result of examining preobese male homozygous mutant mice to investigate with the exclusion of the effect of obesity, hyperphagia with hyperleptinemina and insulin resistance caused by decreased glucose uptake in skeletal muscle were already observed, but the increased hepatic glucose production was not. To investigate whether the insulin resistance was caused by deletion of the Il33 gene, we treated these preobese homozygous mutant mice with recombinant IL-33 protein and noted a significant improvement in insulin resistance. Thus, insulin resistance in these homozygous mutant mice was caused, at least in part, by IL-33 deficiency, suggesting a favorable role of IL-33 for glucose metabolism in the skeletal muscle.
The landscape of somatic mutation in normal colorectal epithelial cells
Authors: Lee-Six Henry , Ellis Peter , Osborne Robert J. , Sanders Mathijs A. , Moore Luiza , Georgakopoulos Nikitas , Torrente Franco , Noorani Ayesha , Goddard Martin , Robinson Philip , Coorens Tim H. H. , O’Neill Laura , Alder Christopher , Wang Jingwei , Fitzgerald Rebecca C. , Zilbauer Matthias , Coleman Nicholas , Saeb-Parsy Kourosh , Martincorena Inigo , Campbell Peter J. , Stratton Michael R.
Published: September 2018

The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions leading to cancer. As for most cancer types, however, understanding of the earliest phases of colorectal neoplastic change, which may occur in morphologically normal tissue, is comparatively limited because of the difficulty of detecting somatic mutations in normal cells. Each colorectal crypt is a small clone of cells derived from a single recently-existing stem cell. Here, we whole genome sequenced hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed, some ubiquitous and continuous, others only found in some individuals, in some crypts or during some phases of the cell lineage from zygote to adult cell. Likely driver mutations were present in ∼1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium.
Complete structural and strain analysis of single GaAs/(In,Ga)As/GaAs core–shell–shell nanowires by means of in-plane and out-of-plane X-ray nanodiffraction
Authors: Al Hassan Ali , Davtyan Arman , Küpers Hanno , Lewis Ryan B. , Bahrami Danial , Bertram Florian , Bussone Genziana , Richter Carsten , Geelhaar Lutz , Pietsch Ullrich
Published: September 2018

Typically, core–shell–shell semiconductor nanowires (NWs) made from III–V materials with low lattice mismatch grow pseudomorphically along the growth axis, i.e. the axial lattice parameters of the core and shell materials are the same. Therefore, both the structural composition and interface strain of the NWs are encoded along directions perpendicular to the growth axis. Owing to fluctuations in the supplied growth species during molecular beam epitaxy (MBE) growth, structural parameters such as local shell thickness, composition and strain may differ between NWs grown onto the same substrate. This requires structural analysis of single NWs instead of measuring NW ensembles. In this work, the complete structure of single GaAs/(In,Ga)As/GaAs core–shell–shell NW heterostructures is determined by means of X-ray nanodiffraction using synchrotron radiation. The NWs were grown by MBE on a prepatterned silicon (111) substrate with a core diameter of 50 nm and an (In,Ga)As shell thickness of 20 nm with a nominal indium concentration of 15%, capped by a 30 nm GaAs outer shell. In order to access single NWs with the X-ray nanobeam being incident parallel to the surface of the substrate, a single row of holes with a separation of 10 µm was defined by electron-beam lithography to act as nucleation centres for MBE NW growth. These well separated NWs were probed sequentially by X-ray nanodiffraction, recording three-dimensional reciprocal-space maps of Bragg reflections with scattering vectors parallel (out-of-plane) and perpendicular (in-plane) to the NW growth axis. From the out-of-plane 111 Bragg reflection, deviations from hexagonal symmetry were derived, together with the diameters of probed NWs grown under the same conditions. The radial NW composition and interface strain became accessible when measuring the two-dimensional scattering intensity distributions of the in-plane 2{\overline 2}0 and 22{\overline 4} reflections, exhibiting well pronounced thickness fringes perpendicular to the NW side planes (truncation rods, TRs). Quantitative values of thickness, composition and strain acting on the (In,Ga)As and GaAs shells were obtained via finite-element modelling of the core–shell–shell NWs and subsequent Fourier transform, simulating the TRs measured along the three different directions of the hexagonally shaped NWs simultaneously. Considering the experimental constraints of the current experiment, thicknesses and In content have been evaluated with uncertainties of ±2 nm and ±0.01, respectively. Comparing data taken from different single NWs, the shell thicknesses differ from one to another.
The influence of human and relational capital on the rapid internationalization of firms
Authors: Baier-Fuentes Hugo , Hormiga Esther , Amorós José Ernesto , Urbano David
Published: September 2018

Purpose

The purpose of this paper is to compare the influence of entrepreneurs’ human and relational capital on the rapid internationalization of their firms from two economically different contexts.

Design/methodology/approach

This study was developed using data that were collected from the Global Entrepreneurship Monitor of Spain and Chile. A logistic regression analysis was used to examine and compare the influence of some elements of entrepreneurs’ human and relational capital on the likelihood of their firms’ rapid internationalization.

Findings

The results revealed that Chilean entrepreneurs rely more on their formal education or experience to rapidly internationalize their firms. In contrast, Spanish entrepreneurs complement their formal education with their relational capital to conduct international entrepreneurial activities.

Research limitations/implications

The implications of this study are related to the role that public policies play in promoting these types of entrepreneurial initiatives.

Originality/value

This study presents several contributions. First, it advances the understanding of entrepreneurial internationalization in emerging economic contexts. Second, it provides a comparative study regarding entrepreneurial internationalization, which is considered a fundamental current in the field of international entrepreneurship. Finally, this comparative study improves our understanding of the influence of different economic contexts on entrepreneurial internationalization.