bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale prediction of binding affinity in protein–small ligand complexes: the PRODIGY-LIG web server
Authors: Vangone Anna , Schaarschmidt Joerg , Koukos Panagiotis , Geng Cunliang , Citro Nevia , Trellet Mikael E , Xue Li C , Bonvin Alexandre M J J
Published: September 2018

Recently we published PROtein binDIng enerGY (PRODIGY), a web-server for the prediction of binding affinity in protein–protein complexes. By using a combination of simple structural properties, such as the residue-contacts made at the interface, PRODIGY has demonstrated a top performance compared with other state-of-the-art predictors in the literature. Here we present an extension of it, named PRODIGY-LIG, aimed at the prediction of affinity in protein-small ligand complexes. The predictive method, properly readapted for small ligand by making use of atomic instead of residue contacts, has been successfully applied for the blind prediction of 102 protein–ligand complexes during the D3R Grand Challenge 2. PRODIGY-LIG has the advantage of being simple, generic and applicable to any kind of protein-ligand complex. It provides an automatic, fast and user-friendly tool ensuring broad accessibility.

Availability and implementation

PRODIGY-LIG is freely available without registration requirements at http://milou.science.uu.nl/services/PRODIGY-LIG.
AbPredict 2: a server for accurate and unstrained structure prediction of antibody variable domains
Authors: Lapidoth Gideon , Parker Jake , Prilusky Jaime , Fleishman Sarel J
Published: September 2018

Methods for antibody structure prediction rely on sequence homology to experimentally determined structures. Resulting models may be accurate but are often stereochemically strained, limiting their usefulness in modeling and design workflows. We present the AbPredict 2 web-server, which instead of using sequence homology, conducts a Monte Carlo-based search for low-energy combinations of backbone conformations to yield accurate and unstrained antibody structures.

Availability and implementation

We introduce several important improvements over the previous AbPredict implementation: (i) backbones and sidechains are now modeled using ideal bond lengths and angles, substantially reducing stereochemical strain, (ii) sampling of the rigid-body orientation at the light-heavy chain interface is improved, increasing model accuracy and (iii) runtime is reduced 20-fold without compromising accuracy, enabling the implementation of AbPredict 2 as a fully automated web-server (http://abpredict.weizmann.ac.il). Accurate and unstrained antibody model structures may in some cases obviate the need for experimental structures in antibody optimization workflows.
Neuronal Distribution Across the Cerebral Cortex of the Marmoset Monkey (Callithrix jacchus)
Authors: Atapour Nafiseh , Majka Piotr , Wolkowicz Ianina H , Malamanova Daria , Worthy Katrina H , Rosa Marcello G P
Published: September 2018

Using stereological analysis of NeuN-stained sections, we investigated neuronal density and number of neurons per column throughout the marmoset cortex. Estimates of mean neuronal density encompassed a greater than 3-fold range, from >150 000 neurons/mm3 in the primary visual cortex to ~50 000 neurons/mm3 in the piriform complex. There was a trend for density to decrease from posterior to anterior cortex, but also local gradients, which resulted in a complex pattern; for example, in frontal, auditory, and somatosensory cortex neuronal density tended to increase towards anterior areas. Anterior cingulate, motor, premotor, insular, and ventral temporal areas were characterized by relatively low neuronal densities. Analysis across the depth of the cortex revealed greater laminar variation of neuronal density in occipital, parietal, and inferior temporal areas, in comparison with other regions. Moreover, differences between areas were more pronounced in the supragranular layers than in infragranular layers. Calculations of the number of neurons per unit column revealed a pattern that was distinct from that of neuronal density, including local peaks in the posterior parietal, superior temporal, precuneate, frontopolar, and temporopolar regions. These results suggest that neuronal distribution in adult cortex result from a complex interaction of developmental/ evolutionary determinants and functional requirements.
How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery Study of Large United States Transplant and Cancer Centers
Authors: Sundermann Alexander J , Clancy Cornelius J , Pasculle A William , Liu Guojun , Cumbie Richard B , Driscoll Eileen , Ayres Ashley , Donahue Lisa , Pergam Steven A , Abbo Lilian , Andes David R , Chandrasekar Pranatharthi , Galdys Alison L , Hanson Kimberly E , Marr Kieren A , Mayer Jeanmarie , Mehta Seema , Morris Michele I , Perfect John , Revankar Sanjay G , Smith Becky , Swaminathan Sankar , Thompson George R , Varghese Merin , Vazquez Jose , Whimbey Estella , Wingard John R , Nguyen M Hong
Published: September 2018

Mucormycosis outbreaks have been linked to contaminated linen. We performed fungal cultures on freshly-laundered linens at 15 transplant and cancer hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%, Mucorales were recovered from >10% of linens. Studies are needed to understand the clinical significance of our findings.
Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines
Authors: Patel Ami , Reuschel Emma L , Kraynyak Kimberly A , Racine Trina , Park Daniel H , Scott Veronica L , Audet Jonathan , Amante Dinah , Wise Megan C , Keaton Amelia A , Wong Gary , Villarreal Daniel O , Walters Jewell , Muthumani Kar , Shedlock Devon J , de La Vega Marc-Antoine , Plyler Ross , Boyer Jean , Broderick Kate E , Yan Jian , Khan Amir S , Jones Shane , Bello Alexander , Soule Geoff , Tran Kaylie N , He Shihua , Tierney Kevin , Qiu Xiangguo , Kobinger Gary P , Sardesai Niranjan Y , Weiner David B
Published: September 2018

Background

There remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations that are unable to receive live-attenuated or viral vector vaccines.

Methods

We designed novel synthetic anti-Ebola virus glycoprotein (EBOV-GP) DNA vaccines as a strategy to expand protective breadth against diverse EBOV strains and evaluated the impact of vaccine dosing and route of administration on protection against lethal EBOV-Makona challenge in cynomolgus macaques. Long-term immunogenicity was monitored in nonhuman primates for >1 year, followed by a 12-month boost.

Results

Multiple-injection regimens of the EBOV-GP DNA vaccine, delivered by intramuscular administration followed by electroporation, were 100% protective against lethal EBOV-Makona challenge. Impressively, 2 injections of a simple, more tolerable, and dose-sparing intradermal administration followed by electroporation generated strong immunogenicity and was 100% protective against lethal challenge. In parallel, we observed that EBOV-GP DNA vaccination induced long-term immune responses in macaques that were detectable for at least 1 year after final vaccination and generated a strong recall response after the final boost.

Conclusions

These data support that this simple intradermal-administered, serology-independent approach is likely important for additional study towards the goal of induction of anti-EBOV immunity in multiple at-risk populations.
Trypomastigote Excretory Secretory Antigen Blot Is Associated With Trypanosoma cruzi Load and Detects Congenital T. cruzi Infection in Neonates, Using Anti–Shed Acute Phase Antigen Immunoglobulin M
Authors: Noazin Sassan , Lee Jessica A , Malaga Edith S , Valencia Ayala Edward , Condori Beth J , Roca Cristian , Lescano Andres G , Bern Caryn , Castillo Walter , Mayta Holger , Menduiña Maria Carmen , Verastegui Manuela R , Tinajeros Freddy , Gilman Robert H ,   Chagas Working Group in Bolivia and Peru, Miranda-Schaeubinger Monica , Chakravarti Indira , Ferriss Ellen L , Chavez Clariza , Velarde Jean Karla , Urquizu Federico , Gorena Mirko , Bowman Natalie , Hinojosa Edith
Published: September 2018

We studied immunoglobulin M–specific shed acute phase antigen bands for diagnosing congenital Chagas disease in newborns. With quantitative polymerase chain reaction as the gold standard, sensitivity was 80%, and specificities were 94% and 100% in areas of endemicity and nonendemicity, respectively.
Gaia DR2 in 6D: searching for the fastest stars in the Galaxy
Authors: Marchetti T , Rossi E M , Brown A G A
Published: September 2018

We search for the fastest stars in the subset of stars with radial velocity measurements of the second data release (DR2) of the European Space Agency mission Gaia. Starting from the observed positions, parallaxes, proper motions, and radial velocities, we construct the distance and total velocity distribution of more than 7 million stars in our Milky Way, deriving the full 6D phase space information in Galactocentric coordinates. These information are shared in a catalogue, publicly available at http://home.strw.leidenuniv.nl/~marchetti/research.html. To search for unbound stars, we then focus on stars with a probability greater than $50 $ per cent of being unbound from the Milky Way. This cut results in a clean sample of 125 sources with reliable astrometric parameters and radial velocities. Of these, 20 stars have probabilities greater than 80 per cent of being unbound from the Galaxy. On this latter subsample, we perform orbit integration to characterize the stars’ orbital parameter distributions. As expected given the relatively small sample size of bright stars, we find no hypervelocity star candidates, stars that are moving on orbits consistent with coming from the Galactic Centre. Instead, we find seven hyperrunaway star candidates, coming from the Galactic disc. Surprisingly, the remaining 13 unbound stars cannot be traced back to the Galaxy, including two of the fastest stars (around 700 km s−1). If conformed, these may constitute the tip of the iceberg of a large extragalactic population or the extreme velocity tail of stellar streams.
Crust or core? Insights from the slow rise of large glitches in the Crab pulsar
Authors: Haskell B , Khomenko V , Antonelli M , Antonopoulou D
Published: September 2018

Pulsar glitches are attributed to the sudden recoupling of weakly coupled superfluid components in the neutron star interior. The transfer of angular momentum between the components is regulated by mutual friction, whose strength defines the spin-up time-scale of a glitch. Hence, observations of glitch rises can be used to shed light on the dominant microphysical interactions at work in the interior of the star. We present a model which naturally produces a fast spin-up followed by a more gradual rise, as observed in large glitches of the Crab pulsar, including the largest recent glitch of 2017. Our model is then used to determine whether the glitch driving region is located in the crust or core of the star. To do this, we compare our results to observations of large glitches in the Crab and Vela pulsars and obtain constraints on the mutual friction parameters that govern the coupling between the superfluid and the crust. Our results are consistent with theoretical estimates for mutual friction in the core for the Vela, but with estimates for the crust in the Crab. This suggests a crustal origin for Crab glitches, but an outer core contribution for Vela glitches.
Up and away: ontogenic transference as a pathway for aerial dispersal of microplastics
Authors: Al-Jaibachi Rana , Cuthbert Ross N. , Callaghan Amanda
Published: September 2018

Microplastics (MPs) are ubiquitous pollutants found in marine, freshwater and terrestrial ecosystems. With so many MPs in aquatic systems, it is inevitable that they will be ingested by aquatic organisms and be transferred up through the food chain. However, to date, no study has considered whether MPs can be transmitted by means of ontogenic transference, i.e. between life stages that use different habitats. Here, we determine whether fluorescent polystyrene beads could transfer betweenCulexmosquito life stages and, particularly, could move into the flying adult stage. We show for the first time that MPs can be transferred ontogenically from a feeding (larva) into a non-feeding (pupa) life stage and subsequently into the adult terrestrial life stage. However, transference is dependent on particle size, with smaller 2 µm MPs transferring readily into pupae and adult stages, while 15 µm MPs transferred at a significantly reduced rate. MPs appear to accumulate in the Malpighian tubule renal excretion system. The transfer of MPs to the adults represents a potential aerial pathway to contamination of new environments. Thus, any organism that feeds on terrestrial life phases of freshwater insects could be impacted by MPs found in aquatic ecosystems.
Multi-lag tone–entropy in neonatal stress
Authors: Šapina Matej , Karmakar Chandan Kumar , Kramarić Karolina , Garcin Matthieu , Adelson P. David , Milas Krešimir , Pirić Marko , Brdarić Dario , Yearwood John
Published: September 2018

Heart rate variability (HRV) has been analysed using linear and nonlinear methods. In the framework of a controlled neonatal stress model, we applied tone–entropy (T–E) analysis at multiple lags to understand the influence of external stressors on healthy term neonates. Forty term neonates were included in the study. HRV was analysed using multi-lag T–E at two resting and two stress phases (heel stimulation and a heel stick blood drawing phase). Higher mean entropy values and lower mean tone values when stressed showed a reduction in randomness with increased sympathetic and reduced parasympathetic activity. A ROC analysis was used to estimate the diagnostic performances of tone and entropy and combining both features. Comparing the resting and simulation phase separately, the performance of tone outperformed entropy, but combining the two in a quadratic linear regression model, neonates in resting as compared to stress phases could be distinguished with high accuracy. This raises the possibility that when applied across short time segments, multi-lag T–E becomes an additional tool for more objective assessment of neonatal stress.
An arc fault diagnosis algorithm using multiinformation fusion and support vector machines
Authors: Yang Jian-hong , Fang Huai-ying , Zhang Ren-cheng , Yang Kai
Published: September 2018

Arc faults in low-voltage electrical circuits are the main hidden cause of electric fires. Accurate identification of arc faults is essential for safe power consumption. In this paper, a detection algorithm for arc faults is tested in a low-voltage circuit. With capacitance coupling and a logarithmic detector, the high-frequency radiation characteristics of arc faults can be extracted. A rapid method for computing the current waveform slope characteristics of an arc fault provides another characteristic. Current waveform periodic integral characteristics can be extracted according to asymmetries of the arc faults. These three characteristics are used to develop a detection algorithm of arc faults based on multiinformation fusion and support vector machine learning models. The tests indicated that for series arc faults with single and combination loads and for parallel arc faults between metallic contacts and along carbonization paths, the recognition algorithm could effectively avoid the problems of crosstalk and signal loss during arc fault detection.
Quantitative correlations between soil and plants in reclaimed mining dumps using a coupling coordination degree model
Authors: Guo Anning , Zhao Zhongqiu , Yuan Ye , Wang Yangyang , Li Xuezhen , Xu Ruicong
Published: September 2018

It is generally accepted that coevolution between soil and plant has great significance for the sustainable development of mining dumps in fragile eco-environment. However, this was not very clear in opencast mine area located in Western China. Based on comprehensive index systems and a combination of subjective and objective weighting method, a coupling coordination degree model, including comprehensive evaluation function, coupling degree and coupling coordination degree, was established to find the ‘short plank’ of different reclamation patterns and to quantify the status quo of coevolution between soil and plant systems in mined plots. The results indicated that only the plot withPinus tabuliformiswas under synchronous development, a mixed model ofRobinia pseudoacacia–Pi. tabuliformisandR. pseudoacaciamonoculture were developed with vegetation lagging, while plotsR. pseudoacacia–Ulmus pumila–Ailanthus altissimaand original landform were soil lagged. All plots were in the state of primary and intermediate coordination. Thus, some effective measures should be taken for the further development in different patterns.
Isolation and structure determination of missing fullerenes Gd@C
74
(CF
3
)

n

through
in situ
trifluoromethylation
Authors: Nakagawa Ayano , Aoyagi Shinobu , Omachi Haruka , Ishino Katsuma , Nishino Makiko , Rio Jeremy , Ewels Chris , Shinohara Hisanori
Published: September 2018

Our trifluoromethyl functionalization method enables the dissolution and isolation of missing metallofullerenes of Gd@C
74
(CF
3
)

n

. After multi-stage high-performance liquid chromatography purification, Gd@C
74
(CF
3
)
3
and two regioisomers of Gd@C
74
(CF
3
) are isolated. X-ray crystallographic analysis reveals that all of the isolated metallofullerenes react with CF
3
groups on pentagons of the
D
3 h
-symmetry C
74
cages. Highest occupied molecular orbital-lowest unoccupied molecular orbital gaps of these trifluoromethylated derivatives, estimated by absorption spectra, are in the range 0.71–1.06 eV, consistent with density functional calculations.
Multi-modal imaging and analysis in the search for iron-based magnetoreceptors in the honeybeeApis mellifera
Authors: Shaw Jeremy A. , Boyd Alastair , House Michael , Cowin Gary , Baer Boris
Published: September 2018

The honeybeeApis melliferais one of many animal species for which empirical evidence of a magnetic sense has been provided. The underlying mechanisms postulated for magnetoreception in bees are varied, but most point towards the abdomen as the most likely anatomical region for its location, partly owing to the large accumulation of iron in trophocyte cells that comprise the honeybee fat body. Using a multi-modal imaging and analysis approach, we have investigated iron in the honeybee, with a particular focus on the abdomen and the utility of such techniques as applied to magnetoreception. Abdominal iron is shown to accumulate rapidly, reaching near maximum levels only 5 days after emerging from the comb and is associated with the accumulation of iron within the fat body. While fat body iron could be visualized, no regions of interest, other than perhaps the fat body itself, were identified as potential sites for magnetoreceptive cells. If an iron-based magnetoreceptor exists within the honeybee abdomen the large accumulation of iron in the fat body is likely to impede its discovery.
Two-dimensional translation-invariant probability distributions: approximations, characterizations and no-go theorems
Authors: Wang Zizhu , Navascués Miguel
Published: September 2018

We study the properties of the set of marginal distributions of infinite translation-invariant systems in the two-dimensional square lattice. In cases where the local variables can only take a small number
d
of possible values, we completely solve the marginal or membership problem for nearest-neighbours distributions (
d
 = 2, 3) and nearest and next-to-nearest neighbours distributions (
d
 = 2). Remarkably, all these sets form convex polytopes in probability space. This allows us to devise an algorithm to compute the minimum energy per site of any TI Hamiltonian in these scenarios exactly. We also devise a simple algorithm to approximate the minimum energy per site up to arbitrary accuracy for the cases not covered above. For variables of a higher (but finite) dimensionality, we prove two no-go results. To begin, the exact computation of the energy per site of arbitrary TI Hamiltonians with only nearest-neighbour interactions is an undecidable problem. In addition, in scenarios with
d
≥2947, the boundary of the set of nearest-neighbour marginal distributions contains both flat and smoothly curved surfaces and the set itself is not semi-algebraic. This implies, in particular, that it cannot be characterized via semidefinite programming, even if we allow the input of the programme to include polynomials of nearest-neighbour probabilities.
Social tipping points in animal societies
Authors: Pruitt Jonathan N. , Berdahl Andrew , Riehl Christina , Pinter-Wollman Noa , Moeller Holly V. , Pringle Elizabeth G. , Aplin Lucy M. , Robinson Elva J. H. , Grilli Jacopo , Yeh Pamela , Savage Van M. , Price Michael H. , Garland Joshua , Gilby Ian C. , Crofoot Margaret C. , Doering Grant N. , Hobson Elizabeth A.
Published: September 2018

Animal social groups are complex systems that are likely to exhibit tipping points—which are defined as drastic shifts in the dynamics of systems that arise from small changes in environmental conditions—yet this concept has not been carefully applied to these systems. Here, we summarize the concepts behind tipping points and describe instances in which they are likely to occur in animal societies. We also offer ways in which the study of social tipping points can open up new lines of inquiry in behavioural ecology and generate novel questions, methods, and approaches in animal behaviour and other fields, including community and ecosystem ecology. While some behaviours of living systems are hard to predict, we argue that probing tipping points across animal societies and across tiers of biological organization—populations, communities, ecosystems—may help to reveal principles that transcend traditional disciplinary boundaries.
High dispersal levels and lake warming are emergent drivers of cyanobacterial community assembly over the Anthropocene in peri-Alpine lakes
Authors: Monchamp Marie-Eve , Spaak Piet , Pomati Francesco
Published: September 2018

Disentangling the relative importance of deterministic and stochastic processes in shaping natural communities is central to ecology. Studies on community assembly over broad temporal and spatial scales in aquatic microorganisms are scarce. Here, we used 16S rDNA sequence data from lake sediments to test for community assembly patterns in cyanobacterial phylogenies across ten European peri-Alpine lakes and over a century of eutrophication and climate warming. We studied phylogenetic similarity in cyanobacterial assemblages over spatial and temporal distance, and environmental gradients, comparing detected patterns with theoretical expectations from deterministic and stochastic processes. We found limited evidence for deviation of lake communities from a random assembly model and no significant effects of geographic distance on phylogenetic similarity, suggesting no dispersal limitation and high levels of stochastic assembly. We did not detect a significant effect of phosphorus and nitrogen levels on deviation of community phylogenies from random. We found however a significant decay of phylogenetic similarity for non-random communities over a gradient of air temperature and water column stability. We show how phylogenetic data from sedimentary archives can improve our understanding of microbial community assembly processes, and support previous evidence that climate warming has been the strongest environmental driver of cyanobacterial community assembly over the Anthropocene.
Disease heritability enrichment of regulatory elements is concentrated in elements with ancient sequence age and conserved function across species
Authors: Hujoel Margaux L.A. , Gazal Steven , Hormozdiari Farhad , van de Geijn Bryce , Price Alkes L.
Published: September 2018

Regulatory elements, e.g. enhancers and promoters, have been widely reported to be enriched for disease and complex trait heritability. We investigated how this enrichment varies with the age of the underlying genome sequence, the conservation of regulatory function across species, and the target gene of the regulatory element. We estimated heritability enrichment by applying stratified LD score regression to summary statistics from 41 independent diseases and complex traits (averageN=320K) and meta-analyzing results across traits. Enrichment of human enhancers and promoters was larger in elements with older sequence age, assessed via alignment with other species irrespective of conserved functionality: enhancer elements with ancient sequence age (older than the split between marsupial and placental mammals) were 8.8x enriched (vs. 2.5x for all enhancers; p = 3e-14), and promoter elements with ancient sequence age were 13.5x enriched (vs. 5.1x for all promoters; p = 5e-16). Enrichment of human enhancers and promoters was also larger in elements whose regulatory function was conserved across species, e.g. human enhancers that were enhancers in ≥5 of 9 other mammals were 4.6x enriched (p = 5e-12 vs. all enhancers). Enrichment of human promoters was larger in promoters of loss-of-function intolerant genes: 12.0x enrichment (p = 8e-15 vs. all promoters). The mean value of several measures of negative selection within these genomic annotations mirrored all of these findings. Notably, the annotations with these excess heritability enrichments were jointly significant conditional on each other and on our baseline-LD model, which includes a broad set of coding, conserved, regulatory and LD-related annotations.
Tissue-expression profiles unveils the gene interaction of hepatopancreas, eyestalk, and ovary in precocious female Chinese mitten crab,Eriocheir sinensis
Authors: Chen Xiaowen , Wang Jun , Hou Xin , Yue Wucheng , Huang Shu , Wang Chenghui
Published: September 2018

Sexual precocity is a serious and common biological phenomenon in animal species. Large amount of precocity individuals was identified in Chinese mitten crab,Eriocheir sinensis, which caused huge economical loss every year. However, the underlying genetic basis of precocity inE. sinensisis still lack. In this study, histology observation, comparative transcriptome was conducted among different stages of precocious one-year old and normal two-year oldE. sinensis, tissue-expression profiles of ovary, hepatopancreas, and eyestalk tissues were presented and compared. Genes associated with lipid metabolic process, lipid transport, vitelline membrane formation, vitelline synthesis and neuropeptide hormone related genes were upregulated in the ovary, hepatopancreas and eyestalk of precociousE. sinensis. Our results indicated eyestalk involved in neuroendocrine system providing neuropeptide hormone that may induce vitellogenesis in hepatopancreas and further stimulate ovary development. Hepatopancreas is a site for energy storage, vitellogenin synthesis and may assist to induce oogenesis through lipid transport in precociousE. sinensis. The genetic basis of precocity inE. sinensisis an integrated gene regulatory network of eyestalk, hepatopancreas, and ovary tissues. Our study provides effective convenient phenotype measurement method for identification of potential precociousE. sinensisdetection, and valuable genetic resources and novel insights into the research of molecular mechanism of precocity inE. sinensis.
Impact of specimen age on its DNA quality for Formalin-Fixed Paraffin-Embedded HPV specimens
Authors: Park James Yeongjun
Published: September 2018

Formalin fixation and paraffin embedding (FFPE) allows the storage of diagnostic and surplus tissue in archival banks. Therefore, FFPE is now a standard method for long-term preservation of tissue biopsies as FFPE of samples preserves the morphology of tissue. Unfortunately, the FFPE process engenders chemical changes and degradation in tissue macromolecules that can pose threats to reliable subsequent analysis. DNA, while more resistant to FFPE in comparison to RNA and protein, is also subject to such chemical formations and degradation. This study provides robust findings about the relationship between DNA quality and specimen age from 10252 FFPE HPV specimens. This paper suggests that there is a perceptible degrading effect in DNA quality as specimens age. This study suggests that the biospecimen may begin to take on new characteristics after certain storage years, and such changes may result in inaccurate determinations of the molecular characteristics of the biospecimen during analysis. Results from this study demonstrate that older HPV specimens are more inclined to be tested negative or inadequate from commercial HPV genotyping assays. Same findings are conferred when multiple genotyping assays are involved with HPV testing. Also, older HPV samples typify fewer HPV types compared to younger HPV samples. The results from this study will be useful to enhance potential scope for next fixation methods such as ethanol fixation that may be equally useful for both molecular profiling and histology as FFPE.
Information and communication technology, mobile devices, and medical education
Authors: Rodríguez-Ríos Andrea , Espinoza-Téllez Gerardo , Martínez-Ezquerro José Darío , Rendón-Macías Mario Enrique
Published: September 2018

Introduction

Information and communication technologies (ICT) are practical and highly available tools. In medical education, ICTs allow physicians to update their knowledge and remember the necessary information within reach of current mobile devices. ICTs as preparation tools for medical education have not been reported for medical students in Mexico.

Methodology

To assess the use of mobile devices as ICTs with medical education purposes, we distributed a questionnaire through an online survey management system to all the medical students (n=180) from a private university in Mexico City, 100% agreed to participate. We developed a questionnaire based on previous surveys and adapted it to our university.

Results

All participants reported possession of an electronic mobile device, and 95% used it regularly for learning purposes. Regardless of the school year, the most frequent usage given to these devices was the search and reading of medical articles, the use of medical calculators, and taking notes. As the levels in career advances, there was a reduction in the use of electronic devices. According to the students, the main barriers towards using mobile devices for learning purposes were both the lack of access to the Internet and permission from the professor to use them.

Conclusion

Most medical students use mobile devices for learning purposes, but usage changes during their education. It is convenient to encourage the use of mobile devices and the development of ICT skills as tools for educational purposes rather than banning their use in schools and hospitals.
Cancer3D 2.0: interactive analysis of 3D patterns of cancer mutations in cancer subsets
Authors: Sedova Mayya , Iyer Mallika , Li Zhanwen , Jaroszewski Lukasz , Post Kai W. , Hrabe Thomas , Porta-Pardo Eduard , Godzik Adam
Published: September 2018

Our knowledge of cancer genomics exploded in last several years, providing us with detailed knowledge of genetic alterations in almost all cancer types. Analysis of this data gave us new insights into molecular aspects of cancer, most important being the amazing diversity of molecular abnormalities in individual cancers. The most important question in cancer research today is how to classify this diversity to identify subtypes that are most relevant for treatment and outcome prediction for individual patients. The Cancer3D database athttp://www.cancer3d.orggives an open and user-friendly way to analyze cancer missense mutations in the context of structures of proteins they are found in and in relation to patients’ clinical data. This approach allows users to find novel candidate driver regions for specific subgroups, that often cannot be found when similar analyses are done on the whole gene level and for large, diverse cohorts. Interactive interface allows user to visualize the distribution of mutations is subgroups defined by cancer type and stage, gender and age brackets, patient’s ethnicity, or vice versa find dominant cancer type, gender or age groups for specific three-dimensional mutation patterns.
Over-expression of Hsp83 in grossly depletedhsrωlncRNA background causes synthetic lethality andl(2)glphenocopy inDrosophila
Authors: Ray Mukulika , Acharya Sundaram , Shambhavi Sakshi , Lakhotia Subhash C.
Published: September 2018

We examined interactions between Hsp83 andhsrωlncRNAs inhsrω66Hsp90GFPhomozygotes, which almost completely lackhsrωlncRNAs but over-express Hsp83. All+/+; hsrω66Hsp90GFPprogeny died before third instar. RareSp/CyO; hsrω66Hsp90GFPreached third instar stage but phenocopiedl(2)glmutants, dying after prolonged larval life, becoming progressively bulbous and transparent with enlarged brain. Additionally, ventral ganglia were elongated. However,hsrω66Hsp90GFP/TM6Bheterozygotes, carrying+/+orSp/CyOsecond chromosomes, developed normally. Total RNA sequencing (+/+, +/+;hsrω66/hsrω66,Sp/CyO; hsrω66/hsrω66,+/+; Hsp90GFP/Hsp90GFP, andSp/CyO; hsrω66Hsp90GFP/hsrω66Hsp90GFPlate third instar larvae) revealed similar effects on many genes inhsrω66andHsp90GFPhomozygotes. Besides additive effect on many of them, numerous additional genes were affected inSp/CyO; hsrω66Hsp90GFPlarvae, withl(2)gland several genes regulating CNS being highly down-regulated in survivingSp/CyO; hsrω66Hsp90GFPlarvae, but not inhsrω66orHsp90GFPsingle mutants. Hsp83 binds at these gene promoters. Several omega speckle associated hnRNPs too may bind with these genes and transcripts. Hsp83-hnRNP interactions are also known. Thus, elevated Hsp83 in altered hnRNP distribution and dynamics, following absence of hsrωlncRNAs and omega speckles, background can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumor suppressor gene likel(2)gl.
Bleaching-independent, whole-cell, 3D and multi-color STED imaging with exchangeable fluorophores
Authors: Spahn Christoph , Grimm Jonathan B. , Lavis Luke D. , Lampe Marko , Heilemann Mike
Published: September 2018

We demonstrate bleaching-independent STED microscopy using fluorogenic labels that reversibly bind to their target structure. A constant exchange of labels guarantees the removal of photobleached fluorophores and their replacement by intact fluorophores, thereby circumventing bleaching-related limitations of STED super-resolution imaging in fixed and living cells. Foremost, we achieve a constant labeling density and demonstrate a fluorescence signal for long and theoretically unlimited acquisition times. Using this concept, we demonstrate whole-cell, 3D, multi-color and live cell STED microscopy with up to 100 min acquisition time.
Pervasive selection against microRNA target sites in human populations
Authors: Hatlen Andrea , Marco Antonio
Published: September 2018

MicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in co-expressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of non-target sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analysed ancestral target sites the derived (non-target) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyse separately target sites in which the target allele is ancestral to the population, the proportion of SNPs with high Fst significantly increases. These findings support population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.
Multiple Toll-Spätzle Pathways in Drosophila melanogaster Immunity
Authors: Chowdhury Munmun , Li Chun-Feng , He Zhen , Lu Yuzhen , Liu Xusheng , Wang Yufeng , Ip Y. Tony , Strand Michael R. , Yu Xiao-Qiang
Published: September 2018

The Drosophila melanogaster Toll-Spätzle pathway plays an important role in development and immunity. Drosophila genome encodes nine Toll receptors and six Spätzle (Spz) proteins, and only the canonical Toll-Spz (Toll-1-Spz-1) pathway has been well investigated. In this study, we compared the nine Drosophila Tolls and showed that similarly to Toll, Toll-7 also strongly activated drosomycin promoter. Importantly, we showed that both Toll and Toll-7 interacted with Spz, Spz-2 and Spz-5, and co-expression of Toll or Toll-7 with Spz, Spz-2 and Spz-5 activated the drosomycin promoter. Furthermore, Toll and Toll-7 both recognized vesicular stomatitis virus (VSV) by binding to the VSV glycoprotein. Septic infection in Toll and Toll-7 mutant flies suggested that Toll and Toll-7 differentially affected defense responses in adult males and females after systemic infection by Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans or VSV. Our results suggest multiple Toll family members activate the expression of antimicrobial peptides. Our results also provide evidence that Toll and Toll-7 bind multiple Spätzle proteins and differentially affect immune defense against different pathogens in adult male and female flies.
A new statistic for efficient detection of repetitive sequences
Authors: Chen Sijie , Sun Fengzhu , Waterman Michael S. , Zhang Xuegong
Published: September 2018

Detecting sequences containing repetitive regions is a basic bioinformatics task with many applications. Several methods have been developed for various types of repeat detection tasks. An efficient generic method for detecting all types of repetitive sequences is still desirable.

Inspired by the excellent properties and successful applications of the D2 family of statistics in comparative analyses of genomic sequences, we developed a new statistic that can efficiently discriminate sequences with or without repetitive regions. Using the statistic, we developed an algorithm of linear complexity in both computation time and memory usage for detecting all types of repetitive sequences in multiple scenarios, including finding candidate CRISPR regions from bacterial genomic or metagenomics sequences. Simulation and real data experiments showed that the method works well on both assembled sequences and unassembled short reads.
Rapid and Repeated Local Adaptation to Climate in an Invasive Plant
Authors: van Boheemen Lotte A. , Atwater Daniel Z. , Hodgins Kathryn A.
Published: September 2018

Biological invasions provide opportunities to study evolutionary processes occurring over contemporary timescales. To explore the speed and repeatability of adaptation, we examined the divergence of life-history traits to climate, using latitude as a proxy, in the native North American and introduced European and Australian ranges of the annual plantAmbrosia artemisiifolia.

We explored niche changes following introductions using climate niche dynamic models. In a common garden, we examined trait divergence by growing seeds collected across three ranges with highly distinct demographic histories. Heterozygosity-fitness associations were used to explore the effect of invasion history on potential success. We accounted for non-adaptive population differentiation using 11,598 SNPs.

We revealed a centroid shift to warmer, wetter climates in the introduced ranges. We identified repeated latitudinal divergence in life-history traits, with European and Australian populations positioned at either end of the native clines.

Our data indicate rapid and repeated adaptation to local climates despite the recent introductions and a bottleneck limiting genetic variation in Australia. Centroid shifts in the introduced ranges suggest adaptation to more productive environments, potentially contributing to trait divergence between the ranges.
Action-specific feature processing in the human visual cortex
Authors: Monaco Simona , Chen Ying , Menghi Nicholas , Crawford J Douglas
Published: September 2018

Sensorimotor integration involves feedforward and reentrant processing of sensory input. Grasp-related motor activity precedes and is thought to influence visual object processing. Yet, while the importance of reentrant feedback is well established in perception, the top-down modulations for action and the neural circuits involved in this process have received less attention. Do action-specific intentions influence the processing of visual information in the human cortex? Using a cue-separation fMRI paradigm, we found that action-specific instruction (manual alignment vs. grasp) influences the cortical processing of object orientation several seconds after the object had been viewed. This influence occurred as early as in the primary visual cortex and extended to ventral and dorsal visual stream areas. Importantly, this modulation was unrelated to non-specific action planning. Further, the primary visual cortex showed stronger functional connectivity with frontal-parietal areas and the inferior temporal cortex during the delay following orientation processing for align than grasping movements, strengthening the idea of reentrant feedback from dorsal visual stream areas involved in action. To our knowledge, this is the first demonstration that intended manual actions have such an early, pervasive, and differential influence on the cortical processing of vision.
ASD Diagnosis in Adults: Phenotype and Genotype Findings from a Clinically-derived Cohort
Authors: Jack F G Underwood , Kimberley M Kendall , Jennifer Berrett , Richard Anney , Marianne B.M. Van den Bree , Jeremy Hall
Published: September 2018

Background

The last decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared to children, little is known about the phenotypic and genetic characteristics of these patients.

Aims

This e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically-presenting sample of adults diagnosed with ASD by specialist services.

Methods

Individuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA. 105 eligible individuals were matched to 76 healthy controls. We investigated the demographics, social history, comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores calculated.

Results

89.5% of individuals with ASD had at least one comorbid psychiatric diagnosis with comorbid depression (62.9%) and anxiety (55.2%) the most common. The ASD group experienced more neurological comorbidities than healthy controls, particularly migraine headache. They were less likely to have married or be in work and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared to controls, but there was no difference in the rate of rare CNVs.

Conclusions

This study provides important information about psychiatric comorbidity in adult ASD which may be used to inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within non-intellectually disabled population of adults with ASD.
The joint evolution of lifespan and self-fertilisation
Authors: Lesaffre Thomas , Billiard Sylvain
Published: September 2018

In Angiosperms, there exists a strong association between mating system and lifespan. Most self-fertilising species are short-lived and most predominant or obligate outcrossers are long-lived. This association is generally explained by the influence of lifespan on the evolution of the mating system, considering lifespan as fixed. Yet, lifespan can itself evolve, and the mating system may as well influence the evolution of lifespan, as is suggested by joint evolutionary shifts of lifespan and mating system between sister species. In this paper, we build modifier models to study the joint evolution of self-fertilisation and lifespan, including both juvenile and adult inbreeding depression. We show that self-fertilisation is expected to promote evolution towards shorter lifespan, and that the range of conditions under which selfing can evolve rapidly shrinks as lifespan increases. We study the effects of inbreeding depression affecting various steps in the life cycle, and discuss how extrinsic mortality conditions are expected to affect evolutionary associations. In particular, we show that selfers may sometimes remain short-lived even in a very stable habitat, as a strategy to avoid the deleterious effects of inbreeding.
Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites.
Authors: Basbous Jihane , Aze Antoine , Chaloin Laurent , Lebdy Rana , Hodroj Dana , Ribeyre Cyril , Larroque Marion , Shepard Caitlin , Kim Baek , Pruvost Alain , Moreaux Jerome , Maiorano Domenico , Mechali Marcel , Constantinou Angelos
Published: September 2018

Imbalance in the level of the pyrimidine degradation products dihydrouracil and dihydrothymine is associated with cellular transformation and cancer progression. Dihydropyrimidines are degraded by dihydropyrimidinase (DHP), a zinc metalloenzyme that is upregulated in solid tumors but not in the corresponding normal tissues. How dihydropyrimidine metabolites affect cellular phenotypes remains elusive. Here we show that the suppression of DHP in cancer cell lines is cytotoxic. An increase in the level of dihydropyrimidines induced DNA replication and transcriptional stress. Cells lacking DHP accumulated DNA-protein crosslinks (DPCs), including covalently trapped DNA polymerase eta. Furthermore, we show that the plant flavonoid dihydromyricetin inhibits human DHP activity. Cellular exposure to dihydromyricetin triggered DPCs-dependent DNA replication stress in cancer cells. This study defines dihydropyrimidines as potentially cytotoxic metabolites that may offer an opportunity for therapeutic-targeting of DHP activity in solid tumors.