bluuebunny/crossref_metadata_2025 huggingface dataset:
Clastic metasediments of the Khamar-Daban Group (Central Asian Orogenic Belt): chemical composition and isotope systematics
Authors: Shkol’nik S.I. , Makrygina V.A.
Published: October 2017

New data have been obtained on major- and trace-element compositions and Sm–Nd isotope systematics of clastic metasediments that belong to the Kornilova and Shubutui Formations in the Khamar-Daban terrane. The Kornilova Formation flysch derived from felsic mature crust, while the Shubutui Formation, with 4.5–7.5 wt.% MgO and higher Cr and Ni contents, had a mafic–ultramafic protolith of an island-arc setting. Isotope data indicate significant inputs of Precambrian crustal material (εNd(T) = –10 to –6.2) to the protolith of the Kornilova rocks and of high amounts of synsedimentary juvenile material to the protolith of the Shubutui Formation (εNd(T) = –2.9 to –1.5). Different model ages (1.7–2.0 and 1.3–1.4 Ga, respectively), compositions, and provenances of the Kornilova and Shubutui rocks, as well as a prolonged deposition gap (>100 Myr), evidence that the two formations were deposited in different basins and tectonic settings. The rock compositions and Nd isotope signatures suggest an island arc setting for the Shubutui deposition in the Dzhida terrane and a continental-margin setting for the deposition of the Kornilova Formation, which is the uppermost straton of the Khamar-Daban terrane.
Unpredictable pain timings lead to greater pain when people are highly intolerant of uncertainty
Authors: Bélanger Clémence , Morin Bernard Blais , Brousseau Andréanne , Gagné Nicolas , Tremblay Anne , Daigle Kathya , Goffaux Philippe , Léonard Guillaume
Published: October 2017

Background and purpose

Many psychological factors are known to influence pain perception. Among them, intolerance of uncertainty (IU) may play a key modulating role in situations where uncertainty prevails, especially uncertainty regarding the timing of painful events. The objective of this study was to explore the impact of individual differences in IUon pain perception during predictable and unpredictable stimulation timings. We hypothesized that people with high IU, as opposed to those with low IU, would perceive more pain when the timing of painful stimulations cannot be predicted, as compared to when they can.

Methods

Twenty (20) healthy adults, aged between 18 and 35 years old, were recruited. Painful sensations were provoked using transcutaneous electrical stimulations of the right sural nerve. By measuring IU (Intolerance of Uncertainty Scale) and subjective pain (verbal numerical rating scale), it was possible to test the relationship between IU and pain perception, by simulating predictable and unpredictable painful experiences. This was done through cued shock interval (CSI) blocks, with either variable timing or fixed timings (long or short time frame). Self-administered questionnaires were also used to measure pain hypervigilance, pain catastrophizing, state anxiety, and trait anxiety.

Results

Pearson correlations confirmed the presence of an association (r = 0.63) between IU and the change in pain intensity provoked by unpredictable stimulation timings. Importantly, this association was significant only for stimulations provided at long CSIs, indicating that higher IU scores predicted higher pain intensity scores when stimulation timings became unpredictable, and when the cued delay was long. No association was found between pain scores and other psychological variables.

Conclusions

Our results show that IU moderately correlates to the change in pain intensity provoked by unpredictable stimulation timings. High IU scores were associated with a worsening of the subjective pain experience, especially during long delays in an unpredictable situation. These observations suggest that IU could be considered as a psychological variable that is able to influence pain perception in certain situations.

Implications

Assessing and addressing IU could be an added value in pain-related therapy, especially in chronic pain.
Understanding a Changing West Antarctic Peninsula
Authors: Hendry Kate , Henley Sian , Schofield Oscar
Published: October 2017

The 1st Workshop of the SOOS WAP Working Group; Cambridge, United Kingdom, 15–16 May 2017
In Icy Waters: The Future of Marine Biogeochemical Research off the West Antarctic Peninsula; Chicheley, United Kingdom, 17–18 May 2017
The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
Authors: Herschhorn Alon , Gu Christopher , Moraca Francesca , Ma Xiaochu , Farrell Mark , Smith Amos B. , Pancera Marie , Kwong Peter D. , Schön Arne , Freire Ernesto , Abrams Cameron , Blanchard Scott C. , Mothes Walther , Sodroski Joseph G.
Published: October 2017

The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally “closed” State 1 to more “open” conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20–β21 element as a major regulator of Env transitions. Several amino acid changes in the β20–β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry.
Recognition of mixed-sequence DNA using double-stranded probes with interstrand zipper arrangements of O2′-triphenylene- and coronene-functionalized RNA monomers
Authors: Karmakar Saswata , Guenther Dale C. , Gibbons Bradley C. , Hrdlicka Patrick J.
Published: October 2017

Energetically activated double-stranded probes with interstrand arrangements of intercalator-functionalized nucleotides enable recognition of mixed-sequence DNA hairpins with excellent binding specificity.
The electronic structure of ε′-V2O5: an expanded band gap in a double-layered polymorph with increased interlayer separation
Authors: Tolhurst Thomas M. , Leedahl Brett , Andrews Justin L. , Banerjee Sarbajit , Moewes Alexander
Published: October 2017

Selective elimination of network connectivity has emerged as an effective means of modifying the electronic structure of materials.
Understanding the mechanism of synthesis of Pt3Co intermetallic nanoparticlesviapreferential chemical vapor deposition
Authors: Saedy S. , Palagin D. , Safonova O. , van Bokhoven J. A. , Khodadadi A. A. , Mortazavi Y.
Published: October 2017

A facile and scalable synthesis method of bimetallic alloyed nanoparticlesviapreferential chemical vapor deposition was developed, leading to a highly active and selective catalyst with a well-defined ordered structure.
Oxygen-dependent generation of a graded polydopamine coating on nanofibrous materials for controlling stem cell functions
Authors: Madhurakkat Perikamana Sajeesh Kumar , Lee Jin Kyu , Shin Young Min , Ahmad Taufiq , Kim Se-jeong , Park Kyung Min , Shin Heungsoo
Published: October 2017

A nanofiber with gradient in polydopamine coating was generated by controlling oxidative polymerization of dopamine for tuning stem cell responses.
Tunable active three‐way circulator using tunable transistor feedback network
Authors: Mung S.W.Y. , Chan W.S.
Published: October 2017

An active three‐way circulator is proposed to have the tunable property by the tunable transistor feedback network (TTFN). This tunable design shows its tunable frequency range from 1.15 to 1.85 GHz (bandwidth of 47%) with the isolation >20 dB, the insertion losses of around 3.5 dB and return losses better than 10 dB at each port at the tuned frequency. This tunable property is controlled by the varactor diodes added at the input and output of the FET in TTFNs.
Lowpass filters with almost‐maximally flat passband and Chebyshev stopband attenuation
Authors: Stamenković N. , Stojanović N. , Krstić I.
Published: October 2017

A class of the almost‐maximally flat (AMF) lowpass filters with Chebyshev stopband attenuation, referred to as AMF filters, is discussed. Allpole lowpass filters’ transfer functions are first derived by using parameters and of modified Jacobi polynomials such that passband attenuation is minimised, and obtained transfer functions are then augmented by adding one or several pairs of ‐axis transmission zeros. The magnitude characteristics of proposed filters are compared with those of the Chebyshev II filters and are found to be superior, both in the passband and in the stopband.
State‐of‐the‐art technologies for UAV inspections
Authors: Jordan Sophie , Moore Julian , Hovet Sierra , Box John , Perry Jason , Kirsche Kevin , Lewis Dexter , Tse Zion Tsz Ho
Published: October 2017

Visual condition inspections serve as the basis for determining the need and schedule for service tasks such as maintenance and remediation projects to preserve the proper functioning of power facilities and infrastructure. An increasing accumulation of service projects has recently surfaced due to the lengthy, labour‐intensive and subjective qualities of the current method for inspection. These processes are also costly due to the temporary closure of the infrastructure as well as the requirement of special inspection equipment. Unmanned aerial vehicles (UAVs), commonly known as drones, offer potential as a useful tool for infrastructure inspections. UAVs provide visual assessments of structures while eliminating the need for manual inspections. Thus, aerial systems have the potential to reduce the cost of inspections as well as limit the disruption of the public while allowing engineers to have a better three‐dimensional understanding of the system. However, the implementation of UAV inspection includes several difficulties such as flight stability, control accuracy, and safety. This study summarises the context for UAV inspection of power facilities and structures. Technologies to address the hindrances preventing UAV integration into the current practice are reviewed. Existing challenges and future work in research for UAV inspections are also presented.
Comparative and verified studies of zirconium nanocomposite nanofibres by bubble spinning
Authors: Li Ya , He Ji‐Huan
Published: October 2017

Zirconia nanocomposite nanofibres were prepared from several different as‐spun fibre polymers fabricated by the bubble spinning, a novel spinning method for mass production of nanofibres. To obtain various zirconia nanocomposites, several polymers were used as zirconia powder carriers for a bubble spinning. The morphology, the thermal/mechanical property and pore‐size distribution of the obtained nanofibres were characterised and the theoretical fluid mechanics analyses were described, then a comparative and verified study drew a conclusion on the distinctions of their principle structural diagrams, resulting in different properties. Among all these nanocomposites, PAN‐based zirconia nanocomposite was found to outperform all the rest nanocomposites, which had the best thermal stability, the most uniform pore structure and the highest strength.
Fabrication of a superhydrophobic poly(vinylidene fluoride) hollow fibre membrane by spray deposition
Authors: Jin Pengrui , Huang Chuan , Li Yifu , Li Jiaxiang , Wang Liao
Published: October 2017

In this work, a poly(vinylidene fluoride) (PVDF) hollow fibre membrane for liquid–gas membrane contactor was coated with a superhydrophobic layer comprising a combination of hydrophobic SiO2 nanoparticles and polydimethylsiloxane. A rough layer of SiO2 deposited on the PVDF membrane resulted in an enhanced surface hydrophobicity. The surface structure of the pristine PVDF significantly affected the homogeneity of the generated SiO2 layer. A uniform surface coating on the PVDF upper layer resulted from the presence of micrometre and nanometre sized roughnesses on the surface of the PVDF membrane, which was achieved with a SiO2 concentration of 4.44 mg ml−1 (0.2 g/45 ml) in the coating solution. As a result, the water contact angle of the modified surface was recorded as 155 ± 3°, which is higher than that of the pristine surface.
Human rights without human supremacism
Authors: Kymlicka Will
Published: October 2017

Early defenders of the Universal Declaration of Human Rights invoked species hierarchy: human beings are owed rights because of our discontinuity with and superiority to animals. Subsequent defenders avoided species supremacism, appealing instead to conditions of embodied subjectivity and corporeal vulnerability we share with animals. In the past decade, however, supremacism has returned in work of the new ‘dignitarians’ who argue that human rights are grounded in dignity, and that human dignity requires according humans a higher status than animals. Against the dignitarians, I argue that defending human rights on the backs of animals is philosophically suspect and politically self-defeating.
Impact of inserted long rest periods during repeated sprint exercise on performance adaptation
Authors: Ikutomo Akiho , Kasai Nobukazu , Goto Kazushige
Published: October 2017

Repeated sprint training consists of a series of brief maximal sprints, 3–7 s in duration, separated by short rest periods of <60 s. However, little is known about the influence of different rest period lengths between sprints on performance adaptation. We determined the influence of inserting long rest periods during repeated sprint training on performance adaptation in competitive athletes. Twenty‐one well‐trained athletes were separated into either the short rest period group (SHORT; n = 10) or the long rest period group (LONG; n = 11). The training protocol for both groups consisted of two sets of 12 × 6‐s maximal cycle sprints with 24 s of rest between sprints. However, in the LONG group, an active rest period of 7 min was inserted every three sprints to attenuate the power output decrement during the latter half of the sprints. The training was performed 3 d/week for 3 weeks. Before and after the training period, repeated sprint ability [12 × 6‐s maximal sprint (pedaling) with 24‐s rest] was evaluated. Maximal power output during the repeated sprint test was significantly increased only in the LONG group (P < .05). Both groups showed a similar increase in power output during the latter half of sprints (P < .05). The LONG group showed a significant increase in (P < .05). These results suggest that repeated sprint training with insertion of longer rest periods is an efficient strategy for improving maximal power output compared with the same training separated by short rest periods alone.
Development of a research-oriented system for collecting mechanical ventilator waveform data
Authors: Rehm Gregory B , Kuhn Brooks T , Delplanque Jean-Pierre , Guo Edward C , Lieng Monica K , Nguyen Jimmy , Anderson Nicholas R , Adams Jason Y
Published: October 2017

Lack of access to high-frequency, high-volume patient-derived data, such as mechanical ventilator waveform data, has limited the secondary use of these data for research, quality improvement, and decision support. Existing methods for collecting these data are obtrusive, require high levels of technical expertise, and are often cost-prohibitive, limiting their use and scalability for research applications. We describe here the development of an unobtrusive, open-source, scalable, and user-friendly architecture for collecting, transmitting, and storing mechanical ventilator waveform data that is generalizable to other patient care devices. The system implements a software framework that automates and enforces end-to-end data collection and transmission. A web-based data management application facilitates nontechnical end users’ abilities to manage data acquisition devices, mitigates data loss and misattribution, and automates data storage. Using this integrated system, we have been able to collect ventilator waveform data from >450 patients as part of an ongoing clinical study.
Case report of the patient source of the Babesia microti R1 reference strain and implications for travelers
Authors: Stahl Philipp , Poinsignon Yves , Pouedras Pascal , Ciubotaru Vasilica , Berry Laurence , Emu Brinda , Krause Peter J , Ben Mamoun Choukri , Cornillot Emmanuel
Published: October 2017

Background

In 2002, a previously healthy 69-year-old man travelled to France from the United States and presented to our hospital with a febrile illness that subsequently was determined to be babesiosis. The blood isolated from this patient served as a source for propagation of the Babesia microti R1 strain with subsequent sequencing and annotation of the parasite genome.

Methods

Upon admission, we obtained a medical history, performed a physical examination, and examined his blood for the presence of a blood borne pathogen by microscopy, PCR and indirect immunofluorescence antibody testing. Once the diagnosis of babesiosis was made, we reviewed the literature to assess the distribution of B. microti-associated babesiosis cases in immunocompetent patients from outside the USA.

Results

The patient recalled a tick bite during the previous month on Cape Cod, Massachusetts. The diagnosis was confirmed by identification of Babesia-infected red blood cells on blood smears, amplification of B. microti DNA in blood by PCR and the presence of B. microti antibody in the serum. This strain was the first isolate of B. microti to be fully sequenced and its annotated genome serves as a reference for molecular and cell biology studies aimed at understanding B. microti pathophysiology and developing diagnostic tests and therapies. A review of babesiosis cases demonstrates a worldwide distribution of B. microti and identifies potential emerging endemic areas where travelers may be at risk of contracting B. microti infection.

Conclusion

This case provides clinical information about the patient infected with the R1 isolate and a review of travel risk, diagnosis and treatment of babesiosis in endemic and non-endemic areas.
Connecting traces of galaxy evolution: the missing core mass–morphological fine structure relation
Authors: Bonfini P , Bitsakis T , Zezas A , Duc P-A , Iodice E , González-Martín O , Bruzual G , González Sanoja A J
Published: October 2017

Deep exposure imaging of early-type galaxies (ETGs) are revealing the second-order complexity of these objects, which have been long considered uniform, dispersion-supported spheroidals. ‘Fine structure’ features (e.g. ripples, plumes, tidal tails, rings) as well as depleted stellar cores (i.e. central light deficits) characterize a number of massive ETG galaxies, and can be interpreted as the result of galaxy–galaxy interactions. We discuss how the time-scale for the evolution of cores and fine structures are comparable, and hence it is expected that they develop in parallel after the major interaction event which shaped the ETG. Using archival data, we compare the ‘depleted stellar mass’ (i.e. the mass missing from the depleted stellar core) against the prominence of the fine structure features, and observe that they correlate inversely. This result confirms our expectation that, while the supermassive black hole (SMBH) binary (constituted by the SMBHs of the merger progenitors) excavates the core via three-body interactions, the gravitational potential of the newborn galaxy relaxes, and the fine structures fade below detection levels. We expect the inverse correlation to hold at least within the first Gyr from the merger which created the SMBH binary; after then, the fine structure evolves independently.
Evolutionary Rescue Over A Fitness Landscape
Authors: Anciaux Yoann , Chevin Luis-Miguel , Ronce Ophélie , Martin Guillaume
Published: October 2017

Evolutionary rescue describes a situation where adaptive evolution prevents the extinction of a population facing a stressing environment. Models of evolutionary rescue could in principle be used to predict the level of stress beyond which extinction becomes likely for species of conservation concern, or conversely the treatment levels most likely to limit the emergence of resistant pests or pathogens. Stress levels are known to affect both the rate of population decline (demographic effect) and the speed of adaptation (evolutionary effect), but the latter aspect has received less attention. Here, we address this issue using Fisher’s Geometric Model of adaptation. In this model, the fitness effects of mutations depend both on the genotype and the environment in which they arise. In particular, the model introduces a dependence between the level of stress, the proportion of rescue mutants, and their costs before the onset of stress. We obtain analytic results under a strong-selection-weak-mutation regime, which we compare to simulations. We show that the effect of the environment on evolutionary rescue can be summarized into a single composite parameter quantifying the effective stress level, which is amenable to empirical measurement. We describe a narrow characteristic stress window over which the rescue probability drops from very likely to very unlikely as the level of stress increases. This drop is sharper than in previous models, as a result of the decreasing proportion of stress-resistant mutations as stress increases. We discuss how to test these predictions with rescue experiments across gradients of stress.
Comparative transcriptome profiling of the human and mouse dorsal root ganglia: An RNA-seq-based resource for pain and sensory neuroscience research
Authors: Ray Pradipta , Torck Andrew , Quigley Lilyana , Wangzhou Andi , Neiman Matthew , Rao Chandranshu , Lam Tiffany , Kim Ji-Young , Hoon Kim Tae , Zhang Michael Q. , Dussor Gregory , Price Theodore J.
Published: October 2017

Molecular neurobiological insight into human nervous tissues is needed to generate next generation therapeutics for neurological disorders like chronic pain. We obtained human Dorsal Root Ganglia (DRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the human DRG (hDRG) transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene co-expression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment. Our analyses reveal an hDRG-enriched protein-coding gene set (~140), some of which have not been described in the context of DRG or pain signaling. A majority of these show conserved enrichment in mDRG, and were mined for known drug - gene product interactions. Comparison of hDRG and tibial nerve transcriptomes suggest pervasive mRNA transport of sensory neuronal genes to axons in adult hDRG, with potential implications for mechanistic insight into chronic pain in patients. Relevant gene families and pathways were also analyzed, including transcription factors (TFs), g-protein coupled receptors (GCPRs) and ion channels. We present our work as an online, searchable repository (http://www.utdallas.edu/bbs/painneurosciencelab/DRGtranscriptome), creating a valuable resource for the community. Our analyses provide insight into DRG biology for guiding development of novel therapeutics, and a blueprint for cross-species transcriptomic analyses.

We generated RNA sequencing data from human DRG samples and comprehensively compared this transcriptome to other human tissues and a matching panel of mouse tissues. Our analysis uncovered functionally enriched genes in the human and mouse DRG with important implications for understanding sensory biology and pain drug discovery.
Haplotype sharing provides insights into fine-scale population history and disease in Finland
Authors: Martin Alicia R. , Karczewski Konrad J. , Kerminen Sini , Kurki Mitja , Sarin Antti-Pekka , Artomov Mykyta , Eriksson Johan G. , Esko Tõnu , Genovese Giulio , Havulinna Aki S. , Kaprio Jaakko , Konradi Alexandra , Korányi László , Kostareva Anna , Männikkö Minna , Metspalu Andres , Perola Markus , Prasad Rashmi B. , Raitakari Olli , Rotar Oxana , Salomaa Veikko , Groop Leif , Palotie Aarno , Neale Benjamin M. , Ripatti Samuli , Pirinen Matti , Daly Mark J.
Published: October 2017

Finland provides unique opportunities to investigate population and medical genomics because of its adoption of unified national electronic health records, detailed historical and birth records, and serial population bottlenecks. We assemble a comprehensive view of recent population history (≤100 generations), the timespan during which most rare disease-causing alleles arose, by comparing pairwise haplotype sharing from 43,254 Finns to geographically and linguistically adjacent countries with different population histories, including 16,060 Swedes, Estonians, Russians, and Hungarians. We find much more extensive sharing in Finns, with at least one ≥ 5 cM tract on average between pairs of unrelated individuals. By coupling haplotype sharing with fine-scale birth records from over 25,000 individuals, we find that while haplotype sharing broadly decays with geographical distance, there are pockets of excess haplotype sharing; individuals from northeast Finland share several-fold more of their genome in identity-by-descent (IBD) segments than individuals from southwest regions containing the major cities of Helsinki and Turku. We estimate recent effective population size changes over time across regions of Finland and find significant differences between the Early and Late Settlement Regions as expected; however, our results indicate more continuous gene flow than previously indicated as Finns migrated towards the northernmost Lapland region. Lastly, we show that haplotype sharing is locally enriched among pairs of individuals sharing rare alleles by an order of magnitude, especially among pairs sharing rare disease causing variants. Our work provides a general framework for using haplotype sharing to reconstruct an integrative view of recent population history and gain insight into the evolutionary origins of rare variants contributing to disease.
An Unexpectedly Complex Architecture for Skin Pigmentation in Africans
Authors: Martin Alicia R , Lin Meng , Granka Julie M , Myrick Justin W , Liu Xiaomin , Sockell Alexandra , Atkinson Elizabeth G , Werely Cedric J , Möller Marlo , Sandhu Manjinder S , Kingsley David M , Hoal Eileen G , Liu Xiao , Daly Mark J , Feldman Marcus W , Gignoux Christopher R , Bustamante Carlos D , Henn Brenna M
Published: October 2017

Fewer than 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed with genetic architecture varying by latitude. We investigate polygenicity in the Khoe and the San, populations indigenous to southern Africa, who have considerably lighter skin than equatorial Africans. We demonstrate that skin pigmentation is highly heritable, but that known pigmentation loci explain only a small fraction of the variance. Rather, baseline skin pigmentation is a complex, polygenic trait in the KhoeSan. Despite this, we identify canonical and non-canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR, and SNX13 using a genome-wide association approach complemented by targeted resequencing. By considering diverse, under-studied African populations, we show how the architecture of skin pigmentation can vary across humans subject to different local evolutionary pressures.
A Deep Recurrent Neural Network Discovers Complex Biological Rules to Decipher RNA Protein-Coding Potential
Authors: Hill Steven T. , Kuintzle Rachael , Teegarden Amy , Merrill Erich , Danaee Padideh , Hendrix David A.
Published: October 2017

The current deluge of newly identified RNA transcripts presents a singular opportunity for improved assessment of coding potential, a cornerstone of genome annotation, and for machine-driven discovery of biological knowledge. While traditional, feature-based methods for RNA classification are limited by current scientific knowledge, deep learning methods can independently discover complex biological rules in the datade novo. We trained a gated recurrent neural network (RNN) on human messenger RNA (mRNA) and long noncoding RNA (lncRNA) sequences. Our model, mRNA RNN (mRNN), surpasses state-of-the-art methods at predicting protein-coding potential. To understand what mRNN learned, we probed the network and uncovered several context-sensitive codons highly predictive of coding potential. Our results suggest that gated RNNs can learn complex and long-range patterns in full-length human transcripts, making them ideal for performing a wide range of difficult classification tasks and, most importantly, for harvesting new biological insights from the rising flood of sequencing data.
An interventional Soylent diet increases theBacteroidetestoFirmicutesratio in human gut microbiome communities: a randomized controlled trial
Authors: Hsu Ryan H. , McCormick Dylan M. , Seitz Mitchell J. , Lui Lauren M. , Rishi Harneet S. , Arkin Adam P.
Published: October 2017

Our knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has been shown to have causative effects on microbiome composition, which can have subsequent implications on health. Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving. This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet. Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits, which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units (OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an individual’s alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary phase. Among Soylent dieters, we find a significant increase in the ratio ofBacteroidetestoFirmicutesabundance, which is associated with several positive health outcomes, including reduced risks of obesity and intestinal inflammation.
Contrasting maternal and paternal genetic variation of hunter-gatherer groups in Thailand
Authors: Kutanan Wibhu , Kampuansai Jatupol , Changmai Piya , Flegontov Pavel , Schröeder Roland , Macholdt Enrico , Hüebner Alexander , Kangwanpong Daoroong , Stoneking Mark
Published: October 2017

The Maniq and Mlabri are the only recorded nomadic hunter-gatherer groups in Thailand. Here, we sequenced complete mitochondrial (mt) DNA genomes and ~2.364 Mbp of non- recombining Y chromosome (NRY) to learn more about the origins of these two enigmatic populations. Both groups exhibited low genetic diversity compared to other Thai populations, and contrasting patterns of mtDNA and NRY diversity: there was greater mtDNA diversity in the Maniq than in the Mlabri, while the converse was true for the NRY. We found basal uniparental lineages in the Maniq, namely mtDNA haplogroups M21a, R21 and M17a, and NRY haplogroup K. Overall, the Maniq are genetically similar to other negrito groups in Southeast Asia. By contrast, the Mlabri haplogroups (B5a1b1 for mtDNA and O1b1a1a1b and O1b1a1a1b1a1 for the NRY) are common lineages in Southeast Asian non-negrito groups, and overall the Mlabri are genetically similar to their linguistic relatives (Htin and Khmu) and other groups from northeastern Thailand. In agreement with previous studies of the Mlabri, our results indicate that the Malbri do not directly descend from the indigenous negritos. Instead, they likely have a recent origin (within the past 1,000 years) by an extreme founder event (involving just one maternal and two paternal lineages) from an agricultural group, most likely the Htin or a closely- related group.
Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination
Authors: Funk Sebastian , Knapp Jennifer K. , Lebo Emmaculate , Reef Susan E. , Dabbagh Alya J. , Kretsinger Katrina , Jit Mark , Edmunds W. John , Strebel Peter M.
Published: October 2017

Background

Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90–95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns.

Methods

We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination.

Results

We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5–9 year olds than established previously.

Conclusions

The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5–9 year olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.
Fitting functional responses: Direct parameter estimation by simulating differential equations
Authors: Rosenbaum Benjamin , Rall Bjoern C.
Published: October 2017

The feeding functional response is one of the most widespread mathematical frameworks in Ecology, Marine Biology, Freshwater Biology, Microbiology and related scientific fields describing the resource-dependent uptake of a consumer. Since the exact knowledge of its parameters is crucial in order to predict, for example, the efficiency of biocontrol agents, population dynamics, food web structure and subsequently biodiversity, a trustful parameter estimation is of utmost importance for scientists using this framework. Classical approaches for estimating functional response parameters lack flexibility and can often only serve as approximation for a correct parameter estimation. Moreover, they do not allow to incorporate side effects such as resource growth or background mortality. Both call for a new method to be established solving these problems. Here, we combined ordinary differential equation models (ODE models), that were numerically solved using computer simulations, with an iterative maximum likelihood fitting approach. We compared our method to classical approaches of fitting functional responses, using data both with and without additional resource growth and mortality. We found that for classical functional response models, like the often used type II and type III functional response, the established fitting methods are reliable. However, using more complex and flexible functional responses, our new established method outperforms the traditional methods. Additionally, only our method allows to analyze experiments correctly when resources experience growth or background mortality. Our method will enable researchers from different scientific fields that are measuring functional responses to estimate parameters correctly. These estimates will enable community ecologists to parameterize their models more precisely, allowing for a deeper understanding of complex ecological systems, and will increase the quality of ecological prediction models.
Identification of genetic factors controlling domestication-related traits in cowpea (Vigna unguiculataL. Walp)
Authors: Lo Sassoum , Muñoz-Amatriaín María , Boukar Ousmane , Herniter Ira , Cisse Ndiaga , Guo Yi-Ning , Roberts Philip A. , Xu Shizhong , Fatokun Christian , Close Timothy J.
Published: October 2017

Cowpea (Vigna unguiculataL. Walp) is a warm-season legume with a genetically diverse gene-pool composed of wild and cultivated forms. Cowpea domestication involved considerable phenotypic changes from the wild progenitor, including reduction of pod shattering, increased organ size, and changes in flowering time. Little is known about the genetic basis underlying these changes. In this study, 215 recombinant inbred lines derived from a cross between a cultivated and a wild cowpea accession were used to evaluate nine domestication-related traits (pod shattering, peduncle length, flower color, flowering time, 100-seed weight, pod length, leaf length, leaf width and seed number per pod). A high-density genetic map containing 17,739 single nucleotide polymorphisms was constructed and used to identify 16 quantitative trait loci (QTL) for these nine domestication-related traits. Candidate genes underlying each of those 16 QTL were identified. Four regions with clusters of QTL were identified, including one on chromosome 8 related to increased organ size. This study provides new knowledge of the genomic regions controlling domestication-related traits in cowpea as well as candidate genes underlying those QTL. This information can help to exploit wild relatives in cowpea breeding programs.

Key message

This study identified regions of the cowpea genome that played an important role in cowpea domestication, including a hotspot region for increased organ size
Morphogen dynamics control patterning in a stem cell model of the human embryo
Authors: Heemskerk Idse , Burt Kari , Miller Matthew , Chhabra Sapna , Guerra M. Cecilia , Warmflash Aryeh
Published: October 2017

During embryonic development, diffusible signaling molecules called morphogens are thought to determine cell fates in a concentration-dependent manner1–4, and protocols for directed stem cell differentiation are based on this picture5–8. However, in the mammalian embryo, morphogen concentrations change rapidly compared to the time for making cell fate decisions9–12. It is unknown how changing ligand levels are interpreted, and whether the precise timecourse of ligand exposure plays a role in cell fate decisions. Nodal and BMP4 are morphogens crucial for gastrulation in vertebrates13. Each pathway has distinct receptor complexes that phosphorylate specific signal transducers, known as receptor-Smads, which then complex with the shared cofactor Smad4 to activate target genes14. Here we show in human embryonic stem cells (hESCs) that the response to BMP4 signaling indeed is determined by the ligand concentration, but that unexpectedly, the expression of many mesodermal targets of Activin/Nodal depends on rate of concentration increase. In addition, we use live imaging of hESCs with GFP integrated at the endogenousSMAD4locus to show that a stem cell model for the human embryo15generates a wave of Nodal signaling. Cells experience rapidly increasing Nodal specifically in the region of mesendoderm differentiation. We also demonstrate that pulsatile stimulation with Activin induces repeated strong signaling and enhances mesoderm differentiation. Our results break with the paradigm of concentration-dependent differentiation and demonstrate an important role for morphogen dynamics in the cell fate decisions associated with mammalian gastrulation. They suggest a highly dynamic picture of embryonic patterning where some cell fates depend on rapid concentration increase rather than absolute levels, and point to ligand dynamics as a new dimension to optimize protocols for directed stem cell differentiation.
Modularity of genes involved in local adaptation to climate despite physical linkage
Authors: Lotterhos Katie E. , Yeaman Sam , Degner Jon , Aitken Sally , Hodgins Kathryn A.
Published: October 2017

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (https://doi.org/10.24072/pci.evolbiol.100050)

Background

Linkage among genes experiencing different selection pressures can make natural selection less efficient. Theory predicts that when local adaptation is driven by complex and non-covarying stresses, increased linkage is favoured for alleles with similar pleiotropic effects, with increased recombination favoured among alleles with contrasting pleiotropic effects. Here, we introduce a framework to test these predictions with a co-association network analysis, which clusters loci based on differing associations. We use this framework to study the genetic architecture of local adaptation to climate in lodgepole pine (Pinus contorta), based on associations with environments.

Results

We identified many clusters of candidate genes and SNPs associated with distinct environments (aspects of aridity, freezing, etc.), and discovered low recombination rates among some candidate genes in different clusters. Only a few genes contained SNPs with effects on more than one distinct aspect of climate. There was limited correspondence between co-association networks and gene regulatory networks. We further showed how associations with environmental principal components can lead to misinterpretation. Finally, simulations illustrated both benefits and caveats of co-association networks.

Conclusions

Our results supported the prediction that different selection pressures favored the evolution of distinct groups of genes, each associating with a different aspect of climate. But our results went against the prediction that loci experiencing different sources of selection would have high recombination among them. These results give new insight into evolutionary debates about the extent of modularity, pleiotropy, and linkage in the evolution of genetic architectures.
Shared High Value Research Resources: The CamCAN Human Lifespan Neuroimaging Dataset Processed on the Open Science Grid
Authors: Krieger Don , Shepard Paul , Zusman Ben , Jana Anirban , Okonkwo David
Published: October 2017

The CamCAN Lifespan Neuroimaging Dataset [1,2], Cambridge (UK) Centre for Ageing and Neuroscience, was acquired and processed beginning in December, 2016. The referee consensus solver deployed to the Open Science Grid [3,4] was used for this task. The dataset includes demographic and screening measures, a high-resolution MRI scan of the brain, and whole-head magnetoencephalographic (MEG) recordings during eyes closed rest (560 sec), a simple task (540 sec), and passive listening/viewing (140 sec). The data were collected from 619 neurologically normal individuals, ages 18-87. The processed results from the resting recordings are completed and available for download at http://stash.osgconnect.net/+krieger/. These constitute ≈1.7 TBytes of data including the location within the brain (1 mm resolution), time stamp (1 msec resolution), and 80 msec time course for each of 3.7 billion validated neuroelectric events, i.e. mean 6.1 million events for each of the 619 participants.

The referee consensus solver provides high yield (mean 11,000 neuroelectric currents/sec; standard deviation (sd): 3500/sec) high confidence (p < 10−12 for each identified current) measures of the neuroelectric currents whose magnetic fields are detected in the MEG recordings. We describe the solver, the implementation of the solver deployed on the Open Science Grid, the workflow management system, the opportunistic use of high performance computing (HPC) resources to add computing capacity to the Open Science Grid reserved for this project, and our initial findings from the recently completed processing of the resting recordings. This required ≈14 million core hours, i.e. ≈40 core hours per second of data.
Passenger mutations can accelerate tumor suppressor gene inactivation in cancer evolution
Authors: Wodarz Dominik , Newell Alan C. , Komarova Natalia L.
Published: October 2017

Carcinogenesis is an evolutionary process whereby cells accumulate multiple mutations. Besides the “driver mutations” that cause the disease, cells also accumulate a number of other mutations with seemingly no direct role in this evolutionary process. They are called passenger mutations. While it has been argued that passenger mutations render tumors more fragile due to reduced fitness, the role of passenger mutations remains understudied. Using evolutionary computational models, we demonstrate that in the context of tumor suppressor gene inactivation (and hence fitness valley crossing), the presence of passenger mutations can accelerate the rate of evolution by reducing overall population fitness and increasing the relative fitness of intermediate mutants in the fitness valley crossing pathway. Hence, the baseline rate of tumor suppressor gene inactivation might be faster than previously thought. Conceptually, parallels are found in the field of turbulence and pattern formation, where instabilities can be driven by perturbations that are damped (disadvantageous), but provide a richer set of pathways such that a system can achieve some desired goal more readily. This highlights, through a number of novel parallels, the relevance of physical sciences in oncology.