bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it Reasonable to Obtain Information on the Polarizability and Hyperpolarizability Only from the Electron Density?
Authors: Jayatilaka Dylan , Jha Kunal K. , Munshi Parthapratim
Published: May 2018

Formulae for the static electronic polarizability and hyperpolarizability are derived in terms of moments of the ground-state electron density matrix by applying the Unsöld approximation and a generalization of the Fermi-Amaldi approximation. The latter formula for the hyperpolarizability appears to be new. The formulae manifestly transform correctly under rotations, and they are observed to be essentially cumulant expressions. Consequently, they are additive over different regions. The properties of the formula are discussed in relation to others that have been proposed in order to clarify inconsistencies. The formulae are then tested against coupled-perturbed Hartree-Fock results for a set of 40 donor-π-acceptor systems. For the polarizability, the correlation is reasonable; therefore, electron density matrix moments from theory or experiment may be used to predict polarizabilities. By constrast, the results for the hyperpolarizabilities are poor, not even within one or two orders of magnitude. The formula for the two- and three-particle density matrices obtained as a side result in this work may be interesting for density functional theories.
National Minorities Under Communism: The Case of Czechoslovakia
Authors: Kalvoda Josef
Published: May 2018

After its establishment in 1918–1919, Czechoslovakia was a multinational state and some of its minorities protested against their being included into it. The nationality problem was related to the collapse of the First Czechoslovak Republic in 1938 and the loss of some of its territories to Germany, Poland, and Hungary. It may be pointed out that the 1920 Constitution did not recognize a separate Slovak national identity and that the Czechs and Slovaks were termed “Czechoslovaks.” The post-Munich Second Republic recognized a separate Slovak nationality; however, the state came to its end in March 1939. In 1945, after its reestablishment as a national state of the Czechs and Slovaks, the country's government attempted to liquidate the national minorities' problem in a drastic manner by transfer (expulsion) of Germans and Hungarians.
Minorities in Hungary Since 1948∗
Authors: Crowe David
Published: May 2018

The uneven course of Hungary's domestic politics and its relations with its socialist neighbors, which have large Magyar populations, has deeply affected the evolution of its minorities' policies since 1948. Initially, the minorities question seemed to be an insignificant issue, since 1949 census figures showed that only 128,758 people out of a total population of 9,204 799 chose something other than Hungarian as their primary language.
NGScloud: RNA-seq analysis of non-model species using cloud computing
Authors: Mora-Márquez Fernando , Vázquez-Poletti José Luis , López de Heredia Unai
Published: May 2018

RNA-seq analysis usually requires large computing infrastructures. NGScloud is a bioinformatic system developed to analyze RNA-seq data using the cloud computing services of Amazon that permit the access to ad hoc computing infrastructure scaled according to the complexity of the experiment, so its costs and times can be optimized. The application provides a user-friendly front-end to operate Amazon’s hardware resources, and to control a workflow of RNA-seq analysis oriented to non-model species, incorporating the cluster concept, which allows parallel runs of common RNA-seq analysis programs in several virtual machines for faster analysis.

Availability and implementation

NGScloud is freely available at https://github.com/GGFHF/NGScloud/. A manual detailing installation and how-to-use instructions is available with the distribution.
Oversight and Ethical Regulation of Conflicts of Interest in Neurosurgery in the United States
Authors: DiRisio Aislyn C , Muskens Ivo S , Cote David J , Babu Maya , Gormley William B , Smith Timothy R , Moojen Wouter A , Broekman Marike L
Published: May 2018

BACKGROUND

Developmental incentives are fundamental to surgical progress, yet financial and professional incentives inherently create conflicts of interest (COI). Understanding how to manage COI held by neurosurgeons, industry, hospitals, and journal editors, without thwarting progress and innovation is critical.

OBJECTIVE

To present an overview of COI associated with innovation in neurosurgery, and review ways to manage these in an ethically sound manner.

METHODS

A review of the literature was performed to assess conflicts of interest that affect neurosurgical innovation, and review ways to manage COI of various parties while adhering to ethical standards.

RESULTS

COI are inherent to collaboration and innovation, and are therefore an unavoidable component of neurosurgery. The lack of a clear distinction between clinical practice and innovation, ability to use devices off-label, and unstandardized disclosure requirements create inconsistencies in the way that conflicts of interest are handled. Additionally, lack of requirements to compare innovation to the standard of care and inherent bias that affects study design and interpretation can have profound effects on the medical literature. Conflicts of interest can have both direct and downstream effects on neurosurgical practice, and it is possible to manage them while improving the quality of research and innovation.

CONCLUSION

Conflicts of interest are inherent to surgical innovation, and can be handled in an ethically sound manner. Neurosurgeons, device companies, hospitals, and medical journals can take steps to proactively confront bias and ensure patient autonomy and safety. These steps can preserve public trust and ultimately improve evidence-based neurosurgical practice.
Redefining Prevention and Care: A Status-Neutral Approach to HIV
Authors: Myers Julie E , Braunstein Sarah L , Xia Qiang , Scanlin Kathleen , Edelstein Zoe , Harriman Graham , Tsoi Benjamin , Andaluz Adriana , Yu Estella , Daskalakis Demetre
Published: May 2018

Recent biomedical advances inspire hope that an end to the epidemic of HIV is in sight. Adopting new approaches and paradigms for treatment and prevention in terms of both messaging and programming is a priority to accelerate progress. Defining the key sequential steps that comprise engagement in HIV care has provided a useful framework for clinical programs and motivated quality improvement initiatives. Recently, the same approach has been applied to use of pre-exposure prophylaxis for HIV prevention. Building on the various prevention and care continua previously proposed, we present a novel schematic that incorporates both people living with HIV and people at risk, making it effectively “status-neutral” in that it proposes the same approach for engagement, regardless of one’s HIV status. This multidirectional continuum begins with an HIV test and offers 2 divergent paths depending on the results; these paths end at a common final state. To illustrate how this continuum can be utilized for program planning as well as for monitoring, we provide an example using data for New York City men who have sex with men, a population with high HIV incidence and prevalence.
Moving like a model: mimicry of hymenopteran flight trajectories by clearwing moths of Southeast Asian rainforests
Authors: Skowron Volponi Marta A. , McLean Donald James , Volponi Paolo , Dudley Robert
Published: May 2018

Clearwing moths are known for their physical resemblance to hymenopterans, but the extent of their behavioural mimicry is unknown. We describe zigzag flights of sesiid bee mimics that are nearly indistinguishable from those of sympatric bees, whereas sesiid wasp mimics display faster, straighter flights more akin to those of wasps. In particular, the flight of the sesiidsHeterosphecia pahangensis,Aschistophleps argentifasciataandPyrophleps cruentataresembles bothTetragonilla collinaandT. atripesstingless bees and, to a lesser extent, dwarf honeybeesApis andreniformis, whereas the sesiidPyrophlepssp. resemblesTachysphexsp. wasps. These findings represent the first experimental evidence for behavioural mimicry in clearwing moths.
Hydrodynamic characteristics of the two-phase flow field at gas-evolving electrodes: numerical and experimental studies
Authors: Liu Cheng-Lin , Sun Ze , Lu Gui-Min , Yu Jian-Guo
Published: May 2018

Gas-evolving vertical electrode system is a typical electrochemical industrial reactor. Gas bubbles are released from the surfaces of the anode and affect the electrolyte flow pattern and even the cell performance. In the current work, the hydrodynamics induced by the air bubbles in a cold model was experimentally and numerically investigated. Particle image velocimetry and volumetric three-component velocimetry techniques were applied to experimentally visualize the hydrodynamics characteristics and flow fields in a two-dimensional (2D) plane and a three-dimensional (3D) space, respectively. Measurements were performed at different gas rates. Furthermore, the corresponding mathematical model was developed under identical conditions for the qualitative and quantitative analyses. The experimental measurements were compared with the numerical results based on the mathematical model. The study of the time-averaged flow field, three velocity components, instantaneous velocity and turbulent intensity indicate that the numerical model qualitatively reproduces liquid motion. The 3D model predictions capture the flow behaviour more accurately than the 2D model in this study.
Selective and metal-free epoxidation of terminal alkenes by heterogeneous polydioxirane in mild conditions
Authors: Kazemnejadi M. , Shakeri A. , Nikookar M. , Shademani R. , Mohammadi M.
Published: May 2018

Polydioxirane (PDOX) was prepared by the treatment of polysalicylaldehyde with Oxone and was found as a selective, highly efficient and heterogeneous reagent for epoxidation of alkenes which can be successfully isolated. This work also introduced a simpler, safer and milder way for epoxidation of alkenes with dioxirane groups than before. PDOX can be simply recovered from the reaction mixture by plain filtration and reused for eight runs without significant reactivity loss.
A helical perylene diimide-based acceptor for non-fullerene organic solar cells: synthesis, morphology and exciton dynamics
Authors: Chen Li , Wu Mingliang , Shao Guangwei , Hu Jiahua , He Guiying , Bu Tongle , Yi Jian-Peng , Xia Jianlong
Published: May 2018

Helical perylene diimide-based (hPDI) acceptors have been established as one of the most promising candidates for non-fullerene organic solar cells (OSCs). In this work, we report a novel hPDI-based molecule, hPDI
2
-CN
2
, as an electron acceptor for OSCs. Combining the hPDI
2
-CN
2
with a low-bandgap polymeric donor (PTB7-Th), the blending film morphology exhibited high sensitivity to various treatments (such as thermal annealing and addition of solvent additives), as evidenced by atomic force microscope studies. The power conversion efficiency (PCE) was improved from 1.42% (as-cast device) to 2.76% after thermal annealing, and a PCE of 3.25% was achieved by further addition of 1,8-diiodooctane (DIO). Femtosecond transient absorption (TA) spectroscopy studies revealed that the improved thin-film morphology was highly beneficial for the charge carrier transport and collection. And a combination of fast exciton diffusion rate and the lowest recombination rate contributed to the best performance of the DIO-treated device. This result further suggests that the molecular conformation needs to be taken into account in the design of perylene diimide-based acceptors for OSCs.
The influences of ammonia on aerosol formation in the ozonolysis of styrene: roles of Criegee intermediate reactions
Authors: Ma Qiao , Lin Xiaoxiao , Yang Chengqiang , Long Bo , Gai Yanbo , Zhang Weijun
Published: May 2018

The influences of ammonia (NH
3
) on secondary organic aerosol (SOA) formation from ozonolysis of styrene have been investigated using chamber experiments and quantum chemical calculations. With the value of [O
3
]
0
/[styrene]
0
ratios between 2 and 4, chamber experiments were carried out without NH
3
or under different [NH
3
]/[styrene]
0
ratios. The chamber experiments reveal that the addition of NH
3
led to significant decrease of SOA yield. The overall SOA yield decreased with the [NH
3
]
0
/[styrene]
0
increasing. In addition, the addition of NH
3
at the beginning of the reaction or several hours after the reaction occurs had obviously different influence on the yield of SOA. Gas phase reactions of Criegee intermediates (CIs) with aldehydes and NH
3
were studied in detail by theoretical methods to probe into the mechanisms behind these phenomena. The calculated results showed that 3,5-diphenyl-1,2,4-trioxolane, a secondary ozonide formed through the reactions of C
6
H
5
ĊHOO· with C
6
H
5
CHO, could make important contribution to the aerosol composition. The addition of excess NH
3
may compete with aldehydes, decreasing the secondary ozonide yield to some extent and thus affect the SOA formation.
The robustness and generalizability of findings on spontaneous false belief sensitivity: a replication attempt
Authors: Schuwerk Tobias , Priewasser Beate , Sodian Beate , Perner Josef
Published: May 2018

Influential studies showed that 25-month-olds and neurotypical adults take an agent's false belief into account in their anticipatory looking patterns (Southgate
et al.
2007
Psychol. Sci.
18
, 587–592 (
doi:10.1111/j.1467-9280.2007.01944.x
); Senju
et al.
2009
Science
325
, 883–885 (
doi:10.1126/science.1176170
)). These findings constitute central pillars of current accounts distinguishing between implicit and explicit Theory of Mind. In our first experiment, which initially included a replication as well as two manipulations, we failed to replicate the original finding in 2- to 3-year-olds (
N
 = 48). Therefore, we ran a second experiment with the sole purpose of seeing whether the effect can be found in an independent, tightly controlled, sufficiently powered and preregistered replication study. This replication attempt failed again in a sample of 25-month-olds (
N
 = 78), but was successful in a sample of adults (
N
 = 115). In all samples, a surprisingly high number of participants did not correctly anticipate the agent's action during the familiarization phase. This led to massive exclusion rates when adhering to the criteria of the original studies and strongly limits the interpretability of findings from the test phase. We discuss both the reliability of our replication attempts as well as the replicability of non-verbal anticipatory looking paradigms of implicit false belief sensitivity, in general.
Microwave-assisted synthesis, computational studies and antibacterial/ anti-inflammatory activities of compounds based on coumarin-pyrazole hybrid
Authors: Chavan Rakesh R. , Hosamani Kallappa M.
Published: May 2018

An efficient, high-yield and rapid synthesis of (E)-1,5-dimethyl-4-((2-((substituted-2-oxo-2H-chromen-4-yl)methoxy)naphthalen-1-yl)methyleneamino)-2-phenyl-1,2-dihydropyrazol-3-one derivatives(3a–3i)containing Schiff base structures under microwave-irradiation has been described. Schiff base is a potential target to discover anti-inflammatory chemotherapeutics, material science, catalysis and molecular magnetism. All the newly synthesized compounds(3a–3i)have been characterized by elemental analysis and spectroscopic techniques. The synthesized compounds(3a–3i)were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compounds(3e)and(3i)exhibit antibacterial effect with minimum inhibitory concentration (MIC) 0.78 µg ml−1and MIC 1.562 µg ml−1against Gram-positiveStaphylococcus aureusbacterial strain compared with standard ciprofloxacin drug (MIC 6.25 µg ml−1). The compounds(3c)and(3f)exhibited an inhibition of heat-induced protein denaturation at the concentration (31.25 µg ml−1) as 53.65% and 67.27%, respectively, and these compounds are more active than standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds withS. aureusdihydropteroate synthetase and results obtained are quite promising.
Synchronized shift of oral, faecal and urinary microbiotas in bats and natural infection dynamics during seasonal reproduction
Authors: Dietrich Muriel , Kearney Teresa , Seamark Ernest C. J. , Paweska Janusz T. , Markotter Wanda
Published: May 2018

Seasonal reproduction is a period of extreme physiological and behavioural changes, yet we know little about how it may affect host microbial communities (i.e. microbiota) and pathogen transmission. Here, we investigated shifts of the bacterial microbiota in saliva, urine and faeces during the seasonal reproduction of bats in South Africa, and test for an interaction in shedding patterns of both bacterial (
Leptospira
) and viral (adeno- and herpesviruses) agents. Based on a comparative approach in two cave-dwelling bat species and high-throughput sequencing of the 16S rRNA gene, we demonstrated a clear signature in microbiota changes over the reproduction season, consistent across the multiple body habitats investigated, and associated with the sex, age and reproductive condition of bats. We observed in parallel highly dynamic shedding patterns for both bacteria and viruses, but did not find a significant association between viral shedding and bacterial microbiota composition. Indeed, only
Leptospira
shedding was associated with alterations in both the diversity and composition of the urinary microbiota. These results illustrate how seasonal reproduction in bats substantially affects microbiota composition and infection dynamics, and have broad implications for the understanding of disease ecology in important reservoir hosts, such as bats.
Polycaprolactone nanofibres loaded with 20(
S
)-protopanaxadiol for
in vitro
and
in vivo
anti-tumour activity study
Authors: Liu Dan-qing , Cheng Zhi-qiang , Feng Qing-jie , Li He-jie , Ye Shu-feng , Teng Bo
Published: May 2018

In this work, 20(
S
)-protopanaxadiol (PPD)-loaded polycaprolactone (PCL) nanofibres were successfully fabricated by the electrospinning technique using Tween 80 as a solubilizer. Firstly, smooth and continuous nanofibres were collected using suitable solvents and appropriate spinning conditions. Secondly, nanofibre mats were characterized by scanning electron microscopy, thermogravimetric (TG) analysis, Fourier transform infrared spectroscopy and mechanical testing. Finally, nanofibrous membranes were evaluated using water contact angle,
in vitro
drug release, biodegradation test,
in vitro
and
in vivo
anti-tumour activity and cell apoptosis assay. Scanning electron microscopic observations indicated that the diameter of the drug-loaded nanofibres increased with the increase of drug concentration. TG analysis and mechanical test showed that nanofibres were equipped with great thermal and mechanical properties. Biodegradation test exhibited that the structure of fabricated nanofibres had a certain degree of change after 15 days. An
in vitro
release study showed that PPD from drug-loaded nanofibres could be released in a sustained and prolonged mode. The cytotoxic effect of drug-loaded nanofibre mats examined on human laryngeal carcinoma cells (Hep-2 cells) demonstrated that the prepared nanofibres had a remarkable anti-tumour effect. Meanwhile, the drug-loaded fibre mats showed a super anti-tumour effect in an
in vivo
anti-tumour study. All in all, PCL nanofibres could be a potential carrier of PPD for cancer treatment.
Sexual selection predicts species richness across the animal kingdom
Authors: Janicke Tim , Ritchie Michael G. , Morrow Edward H. , Marie-Orleach Lucas
Published: May 2018

Our improving knowledge of the animal tree of life consistently demonstrates that some taxa diversify more rapidly than others, but what contributes to this variation remains poorly understood. An influential hypothesis proposes that selection arising from competition for mating partners plays a key role in promoting speciation. However, empirical evidence showing a link between proxies of this sexual selection and species richness is equivocal. Here, we collected standardized metrics of sexual selection for a broad range of animal taxa, and found that taxonomic families characterized by stronger sexual selection on males show relatively higher species richness. Thus, our data support the hypothesis that sexual selection elevates species richness. This could occur either by promoting speciation and/or by protecting species against extinction.
Urea hydrolysis by gut bacteria in a hibernating frog: evidence for urea-nitrogen recycling in Amphibia
Authors: Wiebler James M. , Kohl Kevin D. , Lee Richard E. , Costanzo Jon P.
Published: May 2018

Gut bacteria that produce urease, the enzyme hydrolysing urea, contribute to nitrogen balance in diverse vertebrates, although the presence of this system of urea-nitrogen recycling in Amphibia is as yet unknown. Our studies of the wood frog (
Rana sylvatica
), a terrestrial species that accrues urea in winter, documented robust urease activity by enteric symbionts and hence potential to recoup nitrogen from the urea it produces. Ureolytic capacity in hibernating (non-feeding) frogs, whose guts hosted an approximately 33% smaller bacterial population, exceeded that of active (feeding) frogs, possibly due to an inductive effect of high urea on urease expression and/or remodelling of the microbial community. Furthermore, experimentally augmenting the host's plasma urea increased bacterial urease activity. Bacterial inventories constructed using 16S rRNA sequencing revealed that the assemblages hosted by hibernating and active frogs were equally diverse but markedly differed in community membership and structure. Hibernating frogs hosted a greater relative abundance and richer diversity of genera that possess urease-encoding genes and/or have member taxa that reportedly hydrolyse urea. Bacterial hydrolysis of host-synthesized urea probably permits conservation and repurposing of valuable nitrogen not only in hibernating
R. sylvatica
but, given urea's universal role in amphibian osmoregulation, also in virtually all Amphibia.
Complex gaze stabilization in mantis shrimp
Authors: Daly Ilse M. , How Martin J. , Partridge Julian C. , Roberts Nicholas W.
Published: May 2018

Almost all animals, regardless of the anatomy of the eyes, require some level of gaze stabilization in order to see the world clearly and without blur. For the mantis shrimp, achieving gaze stabilization is unusually challenging as their eyes have an unprecedented scope for movement in all three rotational degrees of freedom: yaw, pitch and torsion. We demonstrate that the speciesOdontodactylus scyllarusperforms stereotypical gaze stabilization in the yaw degree of rotational freedom, which is accompanied by simultaneous changes in the pitch and torsion rotation of the eye. Surprisingly, yaw gaze stabilization performance is unaffected by both the torsional pose and the rate of torsional rotation of the eye. Further to this, we show, for the first time, a lack of a torsional gaze stabilization response in the stomatopod visual system. In the light of these findings, we suggest that the neural wide-field motion detection network in the stomatopod visual system may follow a radially symmetric organization to compensate for the potentially disorientating effects of torsional eye movements, a system likely to be unique to stomatopods.
Interaction between Retinoschisin and Norrin: Physical or Functional Relationship?
Authors: Sudha Dhandayuthapani , Chidambaram Subbulakshmi , Arunachalam Jayamuruga Pandian
Published: May 2018

Background

Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations inRS1andNDPgenes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping clinical features of Norrie disease and retinoschisis in aNDPknock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular mechanism and relationship between the two disorders have still not been understood.

Objective

In this study, we aim to investigate the association between retinoschisin (RS1) and norrin (NDP) usingin vitroandin silicoapproaches.

Method

Specific protein-protein interaction between RS1 and NDP was determined in human retina by co-immunoprecipitation assay and immunoblotting. The immunoprecipitated complexes of RS1 and NDP were analyzed using MALDI-TOF mass spectrometry to validate the findings. STRING database was used to explore the functional relationship.

Results

Co-immunoprecipitation and immunoblotting demonstrated lack of a direct interaction between RS1 and NDP. This was further substantiated by analyzing the immunoprecipitation complexes using MALDI-TOF mass spectrometry. STRING did not reveal any direct functional association between the two proteins.

Conclusion

While literature suggest the existence of digenic involvement ofRS1andNDPin the pathophysiology of retinoschisis and Norrie disease, our data provides evidence for lack of a physical interaction between the two proteins. However, we cannot exclude the possibility of an indirect functional association as our analyses point to MAP kinase signaling pathway, which is presumed to be the link between them.
Large-scale experimental removal of non-native slider turtles has unexpected consequences on basking behavior for both conspecifics and a native, threatened turtle
Authors: Lambert Max R. , McKenzie Jennifer M. , Screen Robyn M. , Clause Adam G. , Johnson Benjamin J. , Mount Genevieve G. , Shaffer H. Bradley , Pauly Gregory B.
Published: May 2018

The red-eared slider turtle (Trachemys scripta elegans; RES) is one of the world’s most invasive species. Native to the central United States, RES are now widely established in freshwater habitats across the globe, largely due to release of unwanted pets. Laboratory and mesocosm experiments suggest that introduced RES are competitively dominant to native turtles, but such competition remains untested in the wild. Here, we experimentally removed introduced RES to test whether they compete for critical basking habitat with native, threatened western pond turtles (Emys marmorata; WPT), a species being considered for listing under the U.S. Endangered Species Act. Following removal, we found that both the remaining RES as well as WPT altered their basking distribution but in a manner inconsistent with strong interspecific competition. However, these findings suggest strong intraspecific competition for basking sites amongst RES and that interspecific competition between WPT and introduced RES likely occurs at higher RES densities. Our works suggests RES influence the behavior of native species in the wild and indicates that RES removal may be most beneficial at high RES densities. This experiment highlights the importance of considering experimental venue when evaluating competition between native and non-native species and should encourage conservation biologists to treat removal efforts as experiments.
Intestinal microbiota of whitefish (Coregonussp.) species pairs and their hybrids in natural and controlled environment
Authors: Sevellec Maelle , Laporte Martin , Bernatchez Alex , Derome Nicolas , Bernatchez Louis
Published: May 2018

It is becoming increasingly clear that wild animals have never existed without symbiotic interactions with microbiota. Therefore, investigating relationships between microbiota and their host is essential towards a full understanding of how animal evolve and adapt to their environment. The Lake Whitefish (Coregonus clupeaformis) is a well-documented model for the study of ecological speciation, where the dwarf species (limnetic niche specialist) evolved independently and repeatedly from the normal species (benthic niche specialist). In this study, we compared the transient intestinal microbiota among five wild sympatric species pairs of whitefish as well as captive representatives of dwarf and normal species and their reciprocal hybrids reared in identical controlled conditions. We sequenced the 16s rRNA gene V3-V4 regions of the transient intestinal microbiota present in a total of 185 whitefish to (i) test for parallelism in the transient intestinal microbiota among sympatric pairs of whitefish, (ii) test for transient intestinal microbiota differences among dwarf, normal and both hybrids reared under identical conditions and (iii) compare intestinal microbiota between wild and captive whitefish. A significant effect of host species on microbiota taxonomic composition was observed in the wild when all lakes where analyzed together, and species effect was observed in three of the five species pairs. In captive whitefish, an influence of host (normal, dwarf and hybrids) was also detected on microbiota taxonomic composition and tens of genera specific to dwarf, normal or hybrids were highlighted. Hybrid microbiota was not intermediate; instead its composition fell outside of that observed in the parental forms and this was observed in both reciprocal hybrid crosses. Interestingly, six genera formed a bacterial core which was present in captive and wild whitefish, suggesting a horizontal microbiota transmission. Although diet appeared to be a major driving force for microbiota evolution, our results suggested a more complex interaction among the host, the microbiota and the environment leading to three distinct evolutionary paths of the intestinal microbiota.
Polyomavirus T-Antigen InducesAPOBEC3BExpression using a LXCXE-Dependent and TP53-Independent Mechanism
Authors: Starrett Gabriel J. , Serebrenik Artur A. , Roelofs Pieter A. , Verhalen Brandy , McCann Jennifer L. , Jarvis Matthew C. , Stewart Teneale A. , Law Emily K , Krupp Annabel , Jiang Mengxi , Martens John W. M. , Span Paul N. , Cahir-McFarland Ellen , Harris Reuben S.
Published: May 2018

APOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomaviruses and papillomaviruses use dominant oncoproteins to induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so. Here we investigate the molecular mechanism of APOBEC3B upregulation by the polyomavirus large T-antigen. First, truncated T-antigen (truncT) is sufficient for APOBEC3B upregulation and the RB interacting motif (LXCXE), but not the TP53 inhibition domain, is required. Second, upregulated APOBEC3B is strongly nuclear and partially localized to virus replication centers. Third, genetic knockdown of RB1 alone or in combination with RBL1 and/or RBL2 is insufficient to suppress truncT-mediated induction ofAPOBEC3B. Fourth, CDK4/6 inhibition by palbociclib is also insufficient to suppress truncT-mediated induction ofAPOBEC3B. Fifth, global gene expression analyses in a wide range of human cancers show significant associations between expression ofAPOBEC3Band other genes known to be regulated by the RB/E2F axis. These experiments combine to implicate the RB/E2F axis in promotingAPOBEC3Btranscription, yet they also suggest that the polyomavirus RB binding motif has in addition to RB inactivation at least one additional function for triggeringAPOBEC3Bupregulation in virus-infected cells.

IMPORTANCE

The APOBEC3B DNA cytosine deaminase is overexpresssed in many different cancers and correlated with elevated frequencies of C-to-T and C-to-G mutations in 5’-TC motifs, oncogene activation, acquired drug resistance, and poor clinical outcomes. The mechanisms responsible for APOBEC3B overexpression are not fully understood. Here, we show that the polyomavirus truncated T-antigen (truncT) triggers APOBEC3B overexpression through its RB-interacting motif, LXCXE, which in turn likely enables one or more E2F family transcription factors to promoteAPOBEC3Bexpression. This work strengthens the mechanistic linkage between active cell cycling, APOBEC3B overexpression, and cancer mutagenesis. Although this mechanism damages cellular genomes, viruses may leverage it to promote evolution, immune escape, and pathogenesis. The cellular portion of the mechanism may also be relevant to non-viral cancers, where genetic mechanisms often activate the RB/E2F axis and APOBEC3B mutagenesis contributes to tumor evolution.
Synthetic-evolution reveals that phosphoregulation of the mitotic kinesin-5 Cin8 is constrained
Authors: Goldstein Alina , Goldman Darya , Valk Ervin , Loog Mart , Holt Liam J. , Gheber Larisa
Published: May 2018

Cdk1 has been found to phosphorylate the majority of its substrates in disordered regions. These phosphorylation sites do not appear to require precise positioning for their function. The mitotic kinesin-5 Cin8 was shown to be phosphoregulated at three Cdk1 sites in disordered loops within its catalytic motor domain. Here, we examined the flexibility of Cin8 phosphoregulation by analyzing the phenotypes of synthetic Cdk1-sites that were systematically generated by single amino-acid substitutions, starting from a phosphodeficient variant of Cin8. Out of 29 synthetic Cdk1 sites that we created, eight were non-functional; 19 were neutral, similar to the phosphodeficient variant; and two gave rise to phosphorylation-dependent spindle phenotypes. Of these two, one site resulted in novel phosphoregulation, and only one site, immediately adjacent to a native Cdk1 site, produced phosphoregulation similar to wild-type. This study shows that, while the gain of a single phosphorylation site can confer regulation and modulate the dynamics of the spindle, to achieve optimal regulation of a mitotic kinesin-5 motor protein, phosphoregulation has to be site-specific and precise.
Effect ofLactobacillus reuterion intestinal microflora and immune parameters: involvement of sex differences
Authors: He Jiayi , Wu Lingyi , Wu Zhen , Pan Daodong , Guo Yuxing , Zeng Xiaoqun , Lian Liwei
Published: May 2018

Probiotic candidateL. reuteriwas screened out forin vivoexperiments based on a relatively higher gastrointestinal tolerance and moderate adhesiveness. As results shown inin-vivoexperiments, a significantly higher level of IL-12 at low-dose group was found both in females and males. Higher levels of T-lymphocytes were also observed in females compared to control group, however, males displayed a reduction expcept for CD8-positive cells in ileum. In comparison to the control group, the relative abundance of phylotypes in the phylumBacteroidetes(genus ofBacteroides,Prevotella) andFirmicutes(genus ofClostridiumIV) exihibited a reserve shift between sexes afterL. reuteriintervened. Meanwhile, the relative abundance of several taxa (Acetobacteroides,Lactobcaillus,bacillus) also differed markedly in sexes at low-dose group, together with microbiota diversity, as indicated by Shannon index.

Importance

Sexual dimorphism has triggered researchers’ attention. However, the relationship between immune parameters and gut microbiota caused byLactobacillusat different dosage are not fully elucidated. In present research, the possible probiotic role ofL. reuteriDMSZ 8533 on immunomodulation and effect on fecal microbiota composition were investigated. Our findings demonstrate the importance of L. reuteri DMSZ 8533 as a potential probiotic strain with an immunomodulatory effect, which also alters the microflora composition depending on the sex of the host.
Protein Docking using Constrained Self-adaptive Differential Evolution Algorithm
Authors: Sudha S. , Baskar S. , Krishnaswamy S.
Published: May 2018

The objective of protein docking is to achieve a relative orientation and an optimized conformation between two proteins that results in a stable structure with the minimized potential energy. Constrained Self-adaptive Differential Evolution (Cons_SaDE) algorithm is used to find the minimum energy conformation using proposed constraints such as boundary surface complementary interactions, non-bonded inter-atomic allowed distances, and finding of interaction and non-interaction sites. With these constraints, Cons_SaDE is efficient enough to explore the promising solutions by gradually self-adapting the strategies and parameters learnt from their previous experiences. Modified sampling scheme called Rotate Only Representation is used to represent a docking conformation. GROMOS53A6 force field is used to find the potential energy. To test the performance of this algorithm, few bound and unbound complexes from Protein Data Bank (PDB) and few easy, medium and difficult complexes from Zlab benchmark4.0 are used. Buried Surface Area, Root Mean Square Deviation (RMSD) and Correlation Coefficient are some of the metrics applied to evaluate the best docked conformations. RMSD values of the best docked conformations obtained from five popular docking web servers are compared with Cons_SaDE results and nonparametric statistical tests for multiple comparisons with control method are implemented to show the performance of this algorithm. Cons_SaDE has produced good quality solutions for the most of the data sets considered.
Differential contributions of subthalamic beta rhythms and neural noise to Parkinson motor symptoms
Authors: Martin Stephanie , Iturrate Iñaki , Chavarriaga Ricardo , Leeb Robert , Sobolewski Aleksander , Li Andrew M. , Zaldivar Julien , Peciu-Florianu Iulia , Pralong Etienne , Castro-Jiménez Mayte , Benninger David , Vingerhoets François , Knight Robert T. , Bloch Jocelyne , Millán José del R.
Published: May 2018

Background

Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson’s disease and associated motor symptoms. However, the relationship between beta activity and motor symptoms has been inconsistent, which may influence the efficacy of closed-loop deep brain stimulation.

Hypothesis

We hypothesized that this variability is due to the degree of neural noise in STN recordings. Recent evidence has shown that neural noise is influenced by multiple factors, such as development, aging and disease, and could confound measures of beta activity. In this work, we propose a model that disentangles beta oscillatory activity and neural noise in the STN power spectrum.

Methods

We investigated the impact of neural noise on estimations of beta activity and motor symptoms from data recorded bilaterally from the subthalamic nuclei of thirteen Parkinsonian patients.

Results

Results showed that the relationship between beta oscillatory amplitude and motor symptoms (bradykinesia and rigidity) significantly improved when neural noise was removed from the estimation of beta activity.

Conclusion

These findings emphasize the importance of modeling neural components independently for understanding physiological processes associated with Parkinson’s disease, and identifying better biomarkers for characterizing symptom severity. Subsequently, we predict that our findings can have a direct application for closed-loop deep brain stimulation on Parkinson’s Disease.
Cryo-EM structures reveal dynamic interplay of nascent chain-processing factors on the ribosome
Authors: Bhakta Sayan , Akbar Shirin , Biswas Chiranjit , Sengupta Jayati
Published: May 2018

During protein biosynthesis in bacteria, one of the earliest phenomena that a nascent polypeptide chain experiences is the co-translational enzymatic processing. The event includes two enzymatic pathways, deformylation of the N-terminal methionine followed by methionine excision catalyzed by peptide deformylase (PDF) and methionine aminopeptidase (MetAP). The ribosome tunnel exit serves as the podium for recruiting proteins involved in maturation processes of the nascent chain. During the process, the emerging nascent protein likely remains shielded by the chaperone trigger factor (TF).

Here, we present the first cryo-EM structures of E. coli ribosome in complex with the nascent chain processing proteins. The structures reveal overlapping binding sites for PDF and MetAP when they bind individually at the tunnel exit site, where proteins L22 and L32 are identified as primary anchoring sites for both proteins. Interestingly however, MetAP has a remarkable ability of repositioning itself to adjacent locations in the presence of PDF and TF at the tunnel exit. Thus, our results disclose an unexpected scanning mechanism that MetAP adopts for context-specific ribosome association.
Circularly shifted filters enable data efficient sequence motif inference with neural networks
Authors: Blum Christopher F. , Kollmann Markus
Published: May 2018

Motivation

Nucleic acids and proteins often have localized sequence motifs that enable highly specific interactions. Due to the biological relevance of sequence motifs, numerous inference methods have been developed. Recently, convolutional neural networks (CNNs) achieved state of the art performance because they can approximate complex motif distributions. These methods were able to learn transcription factor binding sites from ChIP-seq data and to make accurate predictions. However, CNNs learn filters that are difficult to interpret, and networks trained on small data sets often do not generalize optimally to new sequences.

Results

Here we present circular filters, a novel convolutional architecture, that contains all circularly shifted variants of the same filter. We motivate circular filters by the observation that CNNs frequently learn filters that correspond to shifted and truncated variants of the true motif. Circular filters enable learning of non-truncated motifs and allow easy interpretation of the learned filters. We show that circular filters improve motif inference performance over a wide range of hyperparameters. Furthermore, we show that CNNs with circular filters perform better at inferring transcription factor binding motifs from ChIP-seq data than conventional CNNs.

Contact

markus.kollmann@hhu.de
simGWAS: a fast method for simulation of large scale case-control GWAS summarystatistics
Authors: Fortune Mary D. , Wallace Chris
Published: May 2018

Motivation

Methods for analysis of GWAS summary statistics have encouraged data sharing and democratised the analysis of different diseases. Ideal validation for such methods is application to simulated data, where some “truth” is known. As GWAS increase in size, so does the computational complexity of such evaluations; standard practice repeatedly simulates and analyses genotype data for all individuals in an example study.

Results

We have developed a novel method based on an alternative approach, directly simulating GWAS summary data, without individual data as an intermediate step. We mathematically derive the expected statistics for any set of causal variants and their effect sizes, conditional upon control haplotype frequencies (available from public reference datasets). Simulation of GWAS summary output can be conducted independently of sample size by simulating random variates about these expected values. Across a range of scenarios, our method, produces very similar output to that from simulating individual genotypes with a substantial gain in speed even for modest sample sizes. Fast simulation of GWAS summary statistics will enable more complete and rapid evaluation of summary statistic methods as well as opening new potential avenues of research in fine mapping and gene set enrichment analysis.

Availability and Implementation

Our method is available under a GPL license as an R package from http://github.com/chr1swallace/simGWAS

Contact

cew54@cam.ac.uk

Supplementary Information

Supplementary Information is appended.
Identifying micro variables contributing to political risks in international construction projects
Authors: Deng Xiaopeng , Low Sui Pheng , Zhao Xianbo , Chang Tengyuan
Published: May 2018

Purpose

The purpose of this paper is to explore the micro-level variables contributing to political risks in international construction projects.

Design/methodology/approach

A total of 25 micro-level variables were identified from the literature review, and a questionnaire survey was performed with 138 professionals from both academia and industry. Then, the Spearman rank correlation was used to test whether there was agreement on ranking between the two respondent groups. Furthermore, the 25 variables were grouped into six underlying factors through the exploratory factor analysis.

Findings

The results indicated that the most critical variables were “project desirability to the host country,” “relationship with governments,” “misconduct of contractors,” “public opposition to the project,” “experiential knowledge of political risks” and “advantageous conditions of contract.” In addition, the opinions within each group were consistent and there was no significant disagreement on the rankings of variables between academics and practitioners. However, the academic and practitioner groups held different opinions on some individual variables. The impact direction of the variables was associated with confusion among the respondents.

Originality/value

The findings presented in this paper can help international construction enterprises effectively manage political risks in international construction projects.
From project partnering towards strategic supplier partnering
Authors: Sundquist Viktoria , Hulthén Kajsa , Gadde Lars Erik
Published: May 2018

Purpose

Partnering has been at the top of the management agenda in the construction industry for many years as a means of improving performance. Previous research shows that partnering has not reached the desired level of strategic partnering, but stopped at project partnering. The purpose of this paper is to provide an analytical framing for transformation from project partnering towards strategic partnering with suppliers.

Design/methodology/approach

The framework is based on two building blocks: a case study of a contractor involved in implementing strategic partnering with four of its suppliers and a literature review dealing with partnering in construction; and models for close and long-term buyer-supplier collaboration in other contexts.

Findings

Transformation towards strategic partnering should preferably be based on extension of project partnering in two dimensions: extension in time through relationship development with suppliers and extension in space through increasing network orientation across projects.

Practical implications

Succeeding with relationship development and network orientation requires contractors to abandon two significant aspects of established construction logic that serve as significant implementation barriers. Competitive bidding in single projects needs to be replaced by collaboration over series of projects. The decentralisation of authority to the project level needs to be supplemented with increasing centralised decision making.

Originality/value

Previous research showed that despite the considerable interest in partnering there is a lack of systematic theorizing of the phenomenon. This paper contributes to theoretical anchoring through the combining of the case study and the literature review in the abductive approach applied.