bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic exposure of Hawaii Island spinner dolphins (Stenella longirostris) to human activities
Authors: Tyne Julian A. , Christiansen Fredrik , Heenehan Heather L. , Johnston David W. , Bejder Lars
Published: October 2018

Habitat selection is strongly influenced by spatial variations in habitat quality and predation risk. Repeated exposure of wildlife to anthropogenic activities in important habitats may affect habitat selection, leading to negative biological consequences. We quantified the cumulative human exposure of a small, genetically isolated and behaviourally constrained spinner dolphin (Stenella longirostris) population, off Hawaii Island, and exposure effects on their daytime cumulative activity budget. Dolphins were exposed to human activities within 100 m for 82.7% of the daytime, with a median duration of 10 min between exposure events. Individual dolphins spent on average 61.7% (s.d. = 6.5) of their daytime resting. Of their total rest time, greater than 90% occurred inside sheltered bays. Despite high levels of human exposure, we did not observe an effect on dolphin resting behaviour. The short intervals between exposure events probably prevent dolphins from returning to a natural resting state before the next event. Consequently, ‘control’ observations may represent a resting behaviour of a more vigilant nature. Chronic levels of exposure to human activities could lead to rest deprivation, displacement from preferred resting habitats and ultimately negative population level effects. These results have implications for new proposed legislation aiming to reduce dolphin exposure to human activities.
Research on the mechanical behaviour of shale based on multiscale analysis
Authors: Han Qiang , Qu Zhan , Ye Zhengyin
Published: October 2018

In view of the difficulty in obtaining the mechanical properties of shale, the multiscale analysis of shale was performed on a shale outcrop from the Silurian Longmaxi Formation in the Changning area, Sichuan Basin, China. The nano-/micro-indentation test is an effective method for multiscale mechanical analysis. In this paper, effective criteria for the shale indentation test were evaluated. The elastic modulus was evaluated at a multiscale and the engineering validation of drilling cuttings was performed. The porosity tests showed that the pore distribution of shale from the nanoscale to macro-pore could be better displayed by the nuclear magnetic resonance test. The micro-scale elastic modulus and hardness increased nonlinearly with the increase in the clay packing density. It was observed that the size effect of the micro-hardness was based on porosity and composition. The partial spalling of shale at the micro-scale could lead to irregular bulges or steps in a load–displacement curve. The elastic modulus of pure clay minerals was 24.2 GPa on the parallel bedding plane and 15.8 GPa on the vertical bedding plane. The contact hardness (pure clay minerals) was 0.51 GPa. The indentation results showed that the micro-elastic modulus of shale obeyed the normal distribution, and the statistical average could predict the macro-mechanical properties effectively. The present work can provide a new way to recognize the mechanical behaviour of shale.
A homogenization result for interacting elastic and brittle media
Authors: Braides Andrea , Causin Andrea , Solci Margherita
Published: October 2018

We consider energies modelling the interaction of two media parameterized by the same reference set, such as those used to study interactions of a thin film with a stiff substrate, hybrid laminates or skeletal muscles. Analytically, these energies consist of a (possibly non-convex) functional of hyperelastic type and a second functional of the same type such as those used in variational theories of brittle fracture, paired by an interaction term governing the strength of the interaction depending on a small parameter. The overall behaviour is described by letting this parameter tend to zero and exhibiting a limit effective energy using the terminology of Gamma-convergence. Such energy depends on a single state variable and is of hyperelastic type. The form of its energy function highlights an optimization between microfracture and microscopic oscillations of the strain, mixing homogenization and high-contrast effects.
Group and kin recognition via olfactory cues in chimpanzees (Pan troglodytes)
Authors: Henkel Stefanie , Setchell Joanna M.
Published: October 2018

Primates were traditionally thought to have a reduced sense of smell. Although there is now evidence that olfaction plays a greater role in primate social life than previously assumed, research on the sense of smell in non-human apes is scarce. Chimpanzees sniff the ground and vegetation on boundary patrols, but the function of this behaviour is unclear. Since chimpanzees are highly territorial and can kill individuals that do not belong to their own community, sniffing might function to gather information about conspecifics, particularly concerning group membership and kinship. To investigate whether chimpanzees recognize group members and kin via olfactory cues, we conducted behavioural bioassays on two groups of chimpanzees at Leipzig Zoo. In a pilot study, we found that chimpanzees responded more strongly to urine than to faeces or body odour. We then presented urine from group members, outgroup individuals and an unscented control in aerated boxes using a simultaneous discrimination task. The first behaviour after a chimpanzee first approached a box was related to olfaction (sniffing, nose within 20 cm, licking) in 83% of cases, highlighting the importance of olfaction as a general investigation mechanism in this species. Chimpanzees sniffed significantly longer at urine stimuli than the control and significantly longer at odours from outgroup individuals than those from group members. Furthermore, the duration of sniffing was positively correlated with relatedness. Our results suggest that chimpanzees use olfactory cues to obtain information about social relationships and fill a gap in our understanding of primate chemical communication.
Rearing a virulent common cuckoo is not extra costly for its only cavity-nesting host
Authors: Samaš Peter , Rutila Jarkko , Honza Marcel , Kysučan Michal , Grim Tomáš
Published: October 2018

Virulent brood parasites refrain from arduous parental care, often kill host progeny and inflict rearing costs upon their hosts. Quantifying the magnitude of such costs across the whole period of care (from incubation through to parasite fledgling independence) is essential for understanding the selection pressures on hosts to evolve antiparasitic defences. Despite the central importance of such costs for our understanding of coevolutionary dynamics, they have not yet been comprehensively quantified in any host of any avian brood parasite. We quantified parasite-rearing costs in common redstarts
Phoenicurus phoenicurus
raising either parasitic common cuckoo
Cuculus canorus
or their own chicks throughout the complete breeding cycle, and used multiple cost parameters for each breeding stage: incubation, brooding and feeding effort; length of parental/host care; parent/host body condition; and heterophil/lymphocyte ratio (stress-level indicator). Contrary to traditional assumptions, rearing the parasite
per se
was not associated with overall higher physiological or physical costs to hosts above the natural levels imposed by efforts to rear their own progeny. The low parasite-rearing costs imposed on hosts may, in part, explain the low levels of known host counter-defences in this unusually frequently parasitized cuckoo host.
Size matters: height, cell number and a person's risk of cancer
Authors: Nunney Leonard
Published: October 2018

The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide more targets for oncogenic somatic mutation. However, this increase is not seen among mammal species of different sizes (Peto's paradox), a paradox argued to be due to larger species evolving added cancer suppression. If this explanation is correct, the cell number effect is still expected within species. Consistent with this, the hazard ratio for overall cancer risk per 10 cm increase in human height (HR
10
) is about 1.1, indicating a 10% increase in cancer risk per 10 cm; however, an alternative explanation invokes an indirect effect of height, with factors that increase cancer risk independently increasing adult height. The data from four large-scale surveillance projects on 23 cancer categories were tested against quantitative predictions of the cell-number hypothesis, predictions that were accurately supported. For overall cancer risk the HR
10
predicted versus observed was 1.13 versus 1.12 for women and 1.11 versus 1.09 for men, suggesting that cell number variation provides a null hypothesis for assessing height effects. Melanoma showed an unexpectedly strong relationship to height, indicating an additional effect, perhaps due to an increasing cell division rate mediated through increasing IGF-I with height. Similarly, only about one-third of the higher incidence of non-reproductive cancers in men versus women can be explained by cell number. The cancer risks of obesity are not correlated with effects of height, consistent with different primary causation. The direct effect of height on cancer risk suggests caution in identifying height-related SNPs as cancer causing.
Estimating apparent survival of songbirds crossing the Gulf of Mexico during autumn migration
Authors: Ward Michael P. , Benson Thomas J. , Deppe Jill , Zenzal Theodore J. , Diehl Robert H. , Celis-Murillo Antonio , Bolus Rachel , Moore Frank R.
Published: October 2018

Many migratory bird species are declining, and the migratory period may limit populations because of the risk in traversing large geographical features during passage. Using automated radio-telemetry, we tracked 139 Swainson's thrushes (Catharus ustulatus) departing coastal Alabama, USA and crossing the Gulf of Mexico to arrive in the Yucatan Peninsula, Mexico during autumn. We estimated apparent survival and examined how extrinsic (weather variables and day of year) and intrinsic (fat load, sex and age) factors influenced survival using a mark-recapture approach. We also examined how favourability of winds for crossing the Gulf varied over the past 25 years. Fat load, day of year and wind profit were important factors in predicting which individuals survived crossing the Gulf. Survival estimates varied with wind profit and fat, but generally, fat birds departing on days with favourable wind profits had an apparent survival probability of greater than 0.90, while lean individuals with no or negative wind profits had less than 0.33. The proportion of favourable nights varied within and among years, but has increased over the last 25 years. While conservation strategies cannot improve extrinsic factors, they can provide opportunities for birds to refuel before crossing large geographical features through protecting and creating high-quality stopover sites.
Computational biomechanical analyses demonstrate similar shell-crushing abilities in modern and ancient arthropods
Authors: Bicknell Russell D. C. , Ledogar Justin A. , Wroe Stephen , Gutzler Benjamin C. , Watson Winsor H. , Paterson John R.
Published: October 2018

The biology of the American horseshoe crab,Limulus polyphemus, is well documented—including its dietary habits, particularly the ability to crush shell with gnathobasic walking appendages—but virtually nothing is known about the feeding biomechanics of this iconic arthropod.Limulus polyphemusis also considered the archetypal functional analogue of various extinct groups with serial gnathobasic appendages, including eurypterids, trilobites and other early arthropods, especiallySidneyia inexpectansfrom the mid-Cambrian (508 Myr) Burgess Shale of Canada. Exceptionally preserved specimens ofS. inexpectansshow evidence suggestive of durophagous (shell-crushing) tendencies—including thick gnathobasic spine cuticle and shelly gut contents—but the masticatory capabilities of this fossil species have yet to be compared with modern durophagous arthropods. Here, we use advanced computational techniques, specifically a unique application of 3D finite-element analysis (FEA), to model the feeding mechanics ofL. polyphemusandS. inexpectans: the first such analyses of a modern horseshoe crab and a fossil arthropod. Results show that mechanical performance of the feeding appendages in both arthropods is remarkably similar, suggesting thatS. inexpectanshad similar shell-crushing capabilities toL. polyphemus. This biomechanical solution to processing shelly food therefore has a history extending over 500 Myr, arising soon after the first shell-bearing animals. Arrival of durophagous predators during the early phase of animal evolution undoubtedly fuelled the Cambrian ‘arms race’ that involved a rapid increase in diversity, disparity and abundance of biomineralized prey species.
A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum
Authors: Seitzman Benjamin A. , Gratton Caterina , Marek Scott , Raut Ryan V. , Dosenbach Nico U.F. , Schlaggar Bradley L. , Petersen Steven E. , Greene Deanna J.
Published: October 2018

An important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011 and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and cerebellum may be underappreciated thus far. Here, we apply a winner-take-all partitioning method to resting-state fMRI data to generate novel functionally-constrained ROIs in the thalamus, basal ganglia, amygdala, hippocampus, and cerebellum. We validate these ROIs in three datasets using several criteria, including agreement with existing literature and anatomical atlases. Further, we demonstrate that combining these ROIs with established cortical ROIs recapitulates and extends previously described functional network organization. This new set of ROIs is made publicly available for general use, including a full list of MNI coordinates and functional network labels.
Microbiota profiling with long amplicons using Nanopore sequencing: full-length 16S rRNA gene and whole rrn operon
Authors: Cusco Anna , Catozzi Carlotta , Vines Joaquim , Sanchez Armand , Francino Olga
Published: October 2018

Background: Profiling microbiome on low biomass samples is challenging for metagenomics since these samples are prone to present DNA from other sources, such as the host or the environment. The usual approach is sequencing specific hypervariable regions of the 16S rRNA gene, which fails to assign taxonomy to genus and species level. Here, we aim to assess long-amplicon PCR-based approaches for assigning taxonomy at the genus and species level. We use Nanopore sequencing with two different markers: full-length 16S rRNA (~1,500 bp) and the whole rrn operon (16S rRNA gene - ITS - 23S rRNA gene; 4,500 bp).
Methods: We sequenced a clinical isolate of Staphylococcus pseudintermedius, two mock communities (HM-783D, Bei Resources; D6306, ZymoBIOMICS) and two pools of low-biomass samples (dog skin). Nanopore sequencing was performed on MinION (Oxford Nanopore Technologies) using 1D PCR barcoding kit. Sequences were pre-processed, and data were analyzed using WIMP workflow on EPI2ME (ONT) or Minimap2 software with rrn database.
Results: Full-length 16S rRNA and the rrn operon retrieved the microbiota composition from the bacterial isolate, the mock communities and the complex skin samples, even at the genus and species level. For Staphylococcus pseudintermedius isolate, when using EPI2ME, the amplicons were assigned to the correct bacterial species in ~98% of the cases with rrn operon as the marker, and ~68% of the cases with 16S rRNA gene respectively. In both skin microbiota samples, we detected many species with an environmental origin. In chin, we found different Pseudomonas species in high abundance, whereas in the dorsal skin there were more taxa with lower abundances.
Conclusions: Both full-length 16S rRNA and the rrn operon retrieved the microbiota composition of simple and complex microbial communities, even from the low-biomass samples such as dog skin. For an increased resolution at the species level, rrn operon would be the best choice.
DNA barcodes for rapid, whole genome, single-molecule analyses
Authors: Wand Nathaniel , Smith Darren A. , Wilkinson Andrew , Rushton Ashleigh , Busby Stephen J. W. , Styles Iain , Neely Robert K.
Published: October 2018

We report an approach for visualizing DNA sequence and using these ‘DNA barcodes’ to search complex mixtures of genomic material for DNA molecules of interest. We demonstrate three applications of this methodology; by identifying specific molecules of interest from a dataset containing gigabasepairs of genome; by straightforward strain-typing of bacteria from such a dataset and, finally, by locating infecting virus molecules in a background of human genomic material. DNA barcodes enable quantitative understanding of complex genome mixtures, on a large scale. As a result of the dense fluorescent labelling of the DNA, individual barcodes of the order 40 kilobase pairs in length can be reliably identified. This means DNA can be prepared for imaging using standard handling and purification techniques. The recorded dataset provides stable physical and electronic records of the total genomic content of a sample that can be readily searched for a molecule or region of interest.
Modelling cancer progression using Mutual Hazard Networks
Authors: Schill Rudolf , Solbrig Stefan , Wettig Tilo , Spang Rainer
Published: October 2018

Motivation

Cancer progresses by accumulating genomic events, such as mutations and copy number alterations, whose chronological order is key to understanding the disease but difficult to observe. Instead, cancer progression models use co-occurence patterns in cross-sectional data to infer epistatic interactions between events and thereby uncover their most likely order of occurence. State-of-the-art progression models, however, are limited by mathematical tractability and only allow events to interact in directed acyclic graphs, to promote but not inhibit subsequent events, or to be mutually exclusive in distinct groups that cannot overlap.

Results

Here we propose Mutual Hazard Networks (MHN), a new Machine Learning algorithm to infer cyclic progression models from cross-sectional data. MHN model events by their spontaneous rate of fixation and by multiplicative effects they exert on the rates of successive events. MHN compared favourably to acyclic models in cross-validated model fit on four datasets tested. In application to the glioblastoma dataset from The Cancer Genome Atlas, MHN proposed a novel interaction in line with consecutive biopsies: IDH1 mutations are early events that promote subsequent fixation of TP53 mutations.

Availability

Implementation and data are available at https://github.com/RudiSchill/MHN.
The impact of tumor stromal architecture on therapy response and clinical progression
Authors: Altrock Philipp M. , Yoon Nara , Bull Joshua A. , Wu Hao , Ruiz-Ramírez Javier , Miroshnychenko Daria , Kimmel Gregory J. , Kim Eunjung , Vander Velde Robert J. , Rejniak Katarzyna , Manley Brandon J. , Spill Fabian , Marusyk Andriy
Published: October 2018

— Advances in molecular oncology research culminated in the development of targeted therapies that act on defined molecular targets either on tumor cells directly (such as inhibitors of oncogenic kinases), or indirectly by targeting the tumor microenvironment (such as anti-angiogenesis drugs). These therapies can induce strong clinical responses, when properly matched to patients. Unfortunately, most targeted therapies ultimately fail as tumors evolve resistance. Tumors consist not only of neoplastic cells, but also of stroma, whereby “stroma” is the umbrella term for non-tumor cells and extracellular matrix (ECM) within the tumor microenvironment, possibly excluding immune cells1. We know that tumor stroma is an important player in the development of resistance. We also know that stromal architecture is spatially complex, differs from patient to patient and changes with therapy. However, to this date we do not understand the link between spatial and temporal changes in stromal architecture and response of tumors to therapy, in space and time. In this project we sought to address this gap of knowledge using a combination of mathematical and statistical modeling, experimental in vivo studies, and analysis of clinical samples in therapies that target tumor cells directly (in lung and breast cancers) and indirectly (in kidney cancer). This knowledge will inform therapy choices and offer new angles for therapeutic interventions. Our main question is: how does spatial architecture of stroma impact the emergence or evolution of resistance to targeted therapies, and how can we use this knowledge clinically?
Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats
Authors: Wethington Darren , Harder Olivia , Uppulury Karthik , Stewart William C. L. , Chen Phylip , King Tiffany , Reynolds Susan D. , Peeples Mark E. , Niewiesk Stefan , Das Jayajit
Published: October 2018

Respiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) culturesin vitroand in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear mixed effects approach revealed a very low rate (average single cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer at later days (>5 d.p.i) in immunosuppressed cotton rats compared to that in non-suppressed cotton ratsin silico.These predictions were in excellent agreement with the experimental results. Our combined approach quantified the importance of the adaptive immune response in suppressing RSV infection in cotton rats, which could be useful in testing RSV vaccine candidates.

Importance

A major difficulty in developing vaccines against RSV infection is our rudimentary understanding of the mechanisms that underlie RSV infection. We addressed this challenge by developing a mechanistic computational model with predictive powers for describing RSV infection kinetics in cotton rats. The model was constructed synergistically within vitroandin vivomeasurements. The combined framework determined an important role for CD8+ T cells responses in reducing RSV titers in cotton rats. The framework can be used to design future experiments to elucidate mechanisms underlying RSV infection and test outcomes for potential vaccine candidates. In addition, estimation of the model parameters provides quantitative values for parameters of biological and clinical interest such as the replication rate of RSV, the death rate of infected cells, and the average number of new infections initiated by a single infected cell.
Simultaneous task-based BOLD-fMRI and [18-F] FDG functional PET for measurement of neuronal metabolism in the human visual cortex
Authors: Jamadar Sharna D , Ward Phillip GD , Li Shenpeng , Sforazzini Francesco , Baran Jakub , Chen Zhaolin , Egan Gary F
Published: October 2018

Studies of task-evoked brain activity are the cornerstone of cognitive neuroscience, and unravel the spatial and temporal brain dynamics of cognition in health and disease. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is one of the most common methods of studying brain function in humans. BOLD-fMRI indirectly infers neuronal activity from regional changes in blood oxygenation and is not a quantitative metric of brain function. Regional variation in glucose metabolism, measured using [18-F] fluorodeoxyglucose positron emission tomography (FDG-PET), provides a more direct and interpretable measure of neuronal activity. However, while the temporal resolution of BOLD-fMRI is in the order of seconds, standard FDG-PET protocols provide a static snapshot of glucose metabolism. Here, we develop a novel experimental design for measurement of task-evoked changes in regional blood oxygenation and glucose metabolism with high temporal resolution. Over a 90-min simultaneous BOLD-fMRI/FDG-PET scan, [18F] FDG was constantly infused to 10 healthy volunteers, who viewed a flickering checkerboard presented in a hierarchical block design. Dynamic task-related changes in blood oxygenation and glucose metabolism were examined with temporal resolution of 2.5sec and 1-min, respectively. Task-related, temporally coherent brain networks of haemodynamic and metabolic connectivity were maximally related in the visual cortex, as expected. Results demonstrate that the hierarchical block design, together with the infusion FDG-PET technique, enabled both modalities to track task-related neural responses with high temporal resolution. The simultaneous MR-PET approach has the potential to provide unique insights into the dynamic haemodynamic and metabolic interactions that underlie cognition in health and disease.
Rapid, Affordable, Collection and Analysis of Bioaerosol Viral Pathogen (Begomoviruses and Whitefly Vectors)
Authors: Hunter Wayne B. , McKenzie Cindy L. , Mitchell Bailey W.
Published: October 2018

Detection of pathogens is critical to monitoring their distribution and spread, and is a key component in the prediction and management of disease epidemiology. Monitoring for pathogens as bioaerosols requires developing techniques which are sensitive, affordable, and time saving before they will have widespread impact. This approach also overcomes private property issues, which are a major pitfall in monitoring diseases in complex agricultural and urban settings. In this study, we have applied an emerging technology of electrostatic sampling to the detection of an insect-transmitted plant pathogen as a bioaerosol. Where insects aggregate in large numbers, as with whiteflies, leafhoppers, psyllids and honey bees, the pathogen (ie. virus or bacteria) becoming aerosolized as thousands of excreta droplets fall from the plants during feeding. Agricultural systems have not fully measured the impact of bioaerosols on disease epidemiology. Electrostatic sampling provides a valuable, affordable, method for monitoring for diseases as bioaerosols, which includes plant, animal and human pathogens. This study shows results which successfully used an electrostatic sampling device to collect an aerosolized begomovirus from the air near whiteflies feeding on virus-infected tomato plants.
Identifying neurophysiological features associated with anesthetic state in newborn mice and humans
Authors: Chini Mattia , Gretenkord Sabine , Kostka Johanna K. , Pöpplau Jastyn A. , Cornelissen Laura , Berde Charles B. , Hanganu-Opatz Ileana L. , Bitzenhofer Sebastian H.
Published: October 2018

One Sentence Summary

Machine learning reveals consistent features of anesthetic states assessed by intracranial recordings in newborn mice and multichannel EEG in human neonates and infants.

Monitoring the hypnotic component of anesthesia during surgeries is critical to prevent intraoperative awareness and reduce adverse side effects. For this purpose, electroencephalographic methods complementing measures of autonomic functions and behavioral responses are in use in clinical practice. However, in human neonates and infants existing methods may be unreliable and the correlation between brain activity and anesthetic depth is still poorly understood. Here, we characterize the effects of different anesthetics on activity of several brain areas in neonatal mice and develop machine learning approaches to identify electrophysiological features predicting inspired or end-tidal anesthetic concentration as a proxy for anesthetic depth. We show that similar features from electroencephalographic recordings can be applied to predict anesthetic concentration in neonatal mice, and human neonates and infants. These results might support a novel strategy to monitor anesthetic depth in human newborns.
Dysregulation of circular RNAs in myotonic dystrophy type 1
Authors: Voellenkle Christine , Perfetti Alessandra , Carrara Matteo , Fuschi Paola , Renna Laura Valentina , Longo Marialucia , Cardani Rosanna , Valaperta Rea , Silvestri Gabriella , Legnini Ivano , Bozzoni Irene , Furling Denis , Gaetano Carlo , Falcone Germana , Meola Giovanni , Martelli Fabio
Published: October 2018

Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponge for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by “back-splicing”, linking covalently 3’- and 5’-ends of exons. Thus, circRNA levels might be deregulated in conditions associated to altered RNA-splicing. Indeed, increasing evidence indicates their role in human diseases. Specifically, myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by expanded CTG-repeats in the DMPK gene, resulting in abnormal mRNA-splicing. In this investigation, circRNAs expressed in DM1 skeletal muscles were identified by analyzing RNA-sequencing data-sets followed by qPCR validation. In muscle biopsies, out of 9 tested, 4 transcripts showed an increased circular fraction: CDYL, HIPK3, RTN4_03 and ZNF609. The circular fraction values correlated positively with skeletal muscle strength and Receiver-Operating-Characteristics curves showed that these four circRNAs allow to distinguish DM1 patients from controls. The identified circRNAs were also detectable in peripheral-blood-mononuclear-cells (PBMCs) and plasma of DM1 patients, but they were not regulated significantly, indicating a tissue-selectivity of the identified modulations. Finally, increased circular fractions of RTN4_03 and ZNF609 were also observed in differentiated myogenic cell lines derived from DM1 patients.
In conclusion, this proof-of-principle study identified circRNA dysregulation in DM1 patients.
Effect of ring topology in a stochastic model for Z-ring dynamics in bacteria
Authors: Sumedha A. Swain , Kumar A. V. A
Published: October 2018

Understanding the mechanisms responsible for dynamics of theZ-ring is important for our understanding of cell division in prokaryotic cells. In this work, we present a minimal stochastic model that qualititatively reproduces observations of polymerization, of formation of dynamic contractile ring that is stable for a long time and of depolymerization shown by FtsZ polymer. We explore different mechanisms for ring breaking and hydrolysis. Hydrolysis is known to regulate the dynamics of other tubulin polymers like microtubules. We find that the presence of the ring allows for an additional mechanism for regulating the dynamics of FtsZ polymers. Ring breaking dynamics in the presence of hydrolysis naturally induce rescue and catastrophe events, irrespective of the mechanism of hydrolysis. Based on our model, we conclude that theZ-ring undergoes random breaking and closing during the process of cell division.
Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions
Authors: Hocher Antoine , Ruault Myriam , Kaferle Petra , Descrimes Marc , Garnier Mickaël , Morillon Antonin , Taddei Angela
Published: October 2018

The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast, fly, and human. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at varying levels in yeast and found that Sir3 spreads into extended silent domains (ESDs), eventually reaching saturation at subtelomeres. We observed the spread of Sir3 into subtelomeric domains associated with specific histone marks in wild-type cells, and stopping at zones of histone mark transitions including H3K79 trimethylation levels. Our study shows that the conserved H3K79 methyltransferase Dot1 is essential in restricting Sir3 spread beyond ESDs, thus ensuring viability upon overexpression of Sir3. Last, our analyses of published data demonstrate how ESDs unveil uncharacterized discrete domains isolating structural and functional subtelomeric features from the rest of the genome. Our work offers a new approach on how to separate subtelomeres from the core chromosome.
Laser-heating system for high-pressure X-ray diffraction at the Extreme Conditions beamline I15 at Diamond Light Source
Authors: Anzellini Simone , Kleppe Annette K. , Daisenberger Dominik , Wharmby Michael T. , Giampaoli Ruggero , Boccato Silvia , Baron Marzena A. , Miozzi Francesca , Keeble Dean S. , Ross Allan , Gurney Stuart , Thompson Jon , Knap Giles , Booth Mark , Hudson Lee , Hawkins Dave , Walter Michael J. , Wilhelm Heribert
Published: October 2018

In this article, the specification and application of the new double-sided YAG laser-heating system built on beamline I15 at Diamond Light Source are presented. This system, combined with diamond anvil cell and X-ray diffraction techniques, allows in situ and ex situ characterization of material properties at extremes of pressure and temperature. In order to demonstrate the reliability and stability of this experimental setup over a wide range of pressure and temperature, a case study was performed and the phase diagram of lead was investigated up to 80 GPa and 3300 K. The obtained results agree with previously published experimental and theoretical data, underlining the quality and reliability of the installed setup.
A modified discrete tomography for improving the reconstruction of unknown multi-gray-level material in the `missing wedge' situation
Authors: Liu Jianhong , Liang Zhiting , Guan Yong , Wei Wenbin , Bai Haobo , Chen Liang , Liu Gang , Tian Yangchao
Published: October 2018

Full angular rotational projections cannot always be acquired in tomographic reconstructions because of the limited space in the experimental setup, leading to the `missing wedge' situation. In this paper, a recovering `missing wedge' discrete algebraic reconstruction technique algorithm (rmwDART) has been proposed to solve the `missing wedge' problem and improve the quality of the three-dimensional reconstruction without prior knowledge of the material component's number or the material's values. By using oversegmentation, boundary extraction and mathematical morphological operations, `missing wedge' artifact areas can be located. Then, in the iteration process, by updating the located areas and regions, high-quality reconstructions can be obtained from the simulations, and the reconstructed images based on the rmwDART algorithm can be obtained from soft X-ray nano-computed tomography experiments. The results showed that there is the potential for discrete tomography.
Ultra-small-angle X-ray photon correlation spectroscopy using the Eiger detector
Authors: Zinn T. , Homs A. , Sharpnack L. , Tinti G , Fröjdh E , Douissard P.-A. , Kocsis M. , Möller J. , Chushkin Y. , Narayanan T.
Published: October 2018

Successful implementation of the single-photon-counting Eiger 500k pixel array detector for sub-millisecond X-ray photon correlation spectroscopy (XPCS) measurements in the ultra-small-angle scattering region is reported. The performance is demonstrated by measuring the dynamics of dilute silica colloids in aqueous solvents when the detector is operated at different counter depths, 4, 8 and 12 bit. In the fastest mode involving 4 bit parallel readout, a stable frame rate of 22 kHz is obtained that enabled measurement of intensity–intensity autocorrelation functions with good statistics down to the 50 µs range for a sample with sufficient scattering power. The high frame rate and spatial resolution together with large number of pixels of the detector facilitate the investigation of sub-millisecond dynamics over a broad length scale by multispeckle XPCS. This is illustrated by an example involving phoretic motion of colloids during the phase separation of the solvent.
Systematic synthesis of a 6-component organic-salt alloy of naftopidil, and pentanary, quaternary and ternary multicomponent crystals
Authors: Dandela Rambabu , Tothadi Srinu , Marelli Udaya Kiran , Nangia Ashwini
Published: October 2018

The single-crystal X-ray structure of a 6-component organic-salt alloy (hexanary) of naftopidil (1) (an active pharmaceutical ingredient) with benzoic acid (2) and four different hydroxy-substituted benzoic acids, i.e. salicylic acid (3), 2,3-dihydroxybenzoic acid (4), 2,4-dihydroxybenzoic acid (5) and 2,6-dihydroxybenzoic acid (6), is reported. The hexanary assembly originates from the observation that the binary salts of naftopidil with the above acids are isostructural. In addition to the 6-component solid, we also describe five 5-component, ten 4-component, and ten 3-component organic-salt alloys of naftopidil (1) with carboxylic acids (2)–(6). These alloys were obtained from different combinations of the acids with the drug. The synthetic design of the multicomponent organic alloys is based on the rationale of geometrical factors (shape and size) and chemical interactions (hydrogen bonds). The common supramolecular synthon in all these crystal structures was the cyclic N+—H...O− and O—H...O hydrogen-bonded motif of R_2^2(9) graph set between the 2-hydroxyammonium group of naftopidil and the carboxylate anion. This ionic synthon is strong and robust, directing the isostructural assembly of naftopidil with up to five different carboxylic acids in the crystal structure together with the lower-level multicomponent adducts. Solution crystallization by slow evaporation provided the multicomponent organic salts and alloys which were characterized by a combination of single-crystal X-ray diffraction, powder X-ray diffraction, NMR and differential scanning calorimetry techniques.
Two new POM-based compounds modified by lanthanide–Schiff base complexes with interesting NLO properties
Authors: Luo Xi-Ming , Cui Chen-Hui , Cao Jia-Peng , Lin Qing-Fang , Xu Yan
Published: October 2018

Two POM-based lanthanide derivatives, namely {triaqua[2,6-diacetylpyridine bis(semicarbazone)-κ5
O,N,N′,N′′,O′]terbium(III)}-μ-oxido-[tricosa-μ2-oxido-dodecaoxido-μ12-phosphato-dodecamolybdenum(VI)] pentahydrate (1), [Tb(C11H15N7O2)(H2O)3][PMo12O40]·5H2O, and the dysprosium(III) analogue (2), have been isolated successfully by the reaction of Keggin–POM [PMo12O40]3− (abbreviated as PMo12
), the Ln3+ ion and the Schiff base 2,6-diacetylpyridine bis(semicarbazone) (DAPSC) ligand under hydrothermal conditions. [Ln(DAPSC)(H2O)3][PMo12O40]·5H2O is a PMo12
-supported cluster featuring a lanthanide–Schiff base complex [denoted Ln–

L

(Schiff base)]. Single-crystal X-ray diffraction analysis reveals that the LnIII ion is in a distorted tricapped trigonal prismatic arrangement, coordinated by six O atoms and three N atoms. Two O atoms and three N atoms are provided by one DAPSC ligand, while the additional O atoms originate from a PMo12
cluster and three water molecules. Hydrogen-bonding interactions between adjacent clusters form an interesting three-dimensional supramolecular structure. The identities of 1 and 2 were characterized by IR spectroscopy, thermogravimetric analysis and powder X-ray diffraction. Interestingly, both compounds possess excellent two-photon absorption (TPA) responses to the third-order nonlinear optics (NLO) (2264 GM for 1 and 941 GM for 2), suggesting that they have potential applications in the field of nonlinear optics (NLO). To our knowledge, 1 and 2 are the first POM-based Ln–

L

(Schiff base) complexes showing excellent two-photon responses. Meanwhile, the electrochemical properties of both compounds were studied in detail.
The study of interactions with a halogen atom: influence of NH2group insertion on the crystal structures ofmeta-bromonitrobenzene derivatives
Authors: Marek Paulina H. , Urban Mateusz , Madura Izabela D.
Published: October 2018

Halogen atoms in molecular crystals may be involved in various interactions, often playing a very important role in structure stabilization. By introducing electron-donating groups, such as NH2, the electron density of the molecule is changed and thus interactions with the bromine substituent may alter. Herein, the crystal structures ofmeta-bromonitrobenzene and its NH2-substituted derivatives are analyzed. In all four described structures, namelym-bromonitrobenzene [Charlton & Trotter (1963).Acta Cryst.16, 313], 4-bromo-2-nitroaniline (C6H5BrN2O2,1), 2-bromo-6-nitroaniline (2) and 2-bromo-4-nitroaniline [Arshadet al.(2009).Acta Cryst.E65, o480], the Br atom is engaged in different interactions (Br...π, Br...O, Br...Br and C—H...Br, respectively). The Hirshfeld surface analysis (HS) and Reduced Density Gradient NonCovalent Interaction (RDG NCI) plots are used to prove the relevance, directionality and stabilizing nature of these interactions. Their modifications have been associated with the position of the amino group in the molecular structure and its influence on charge distribution analyzed with electrostatic potential surfaces (EPS). The diversification of the interactions has been correlated with a σ-hole potential value that enables a switching of the Br-atom character from electrophilic to nucleophilic.
Low-dimensional compounds containing cyanido groups. Part XXXV. Structure, spectral, thermal and magnetic properties of a binuclear CuII–biquinoline complex with bridging and terminal dicyanamide ligands
Authors: Potočňák Ivan , Bukrynov Oleksandr , Ráczová Katarína , Čižmár Erik , Vitushkina Svitlana , Váhovská Lucia , Dušek Michal , Štarha Pavel
Published: October 2018

From the system CuCl2–biq–NaN(CN)2(biq is 2,2′-biquinoline), the binuclear molecular complex bis(μ-dicyanamido-κ2N1:N5)bis[(2,2′-biquinoline-κ2N,N′)(dicyanamido-κN1)copper(II)], [Cu2(C2N3)4(C18H12N2)2] or [Cu2(biq)2(dca)2(μ1,5-dca)2] (1) [dca is dicyanamide, N(CN)2−] was isolated and characterized by crystal structure analysis, and spectral, thermal and magnetic measurements. IR spectroscopy confirmed the presence of the biq and dca ligands in1. Its solid-state structure consists of discrete centrosymmetric binuclear copper(II) units with double end-to-end dca bridges. Each CuIIatom is in a distorted square-pyramidal environment with the equatorial plane formed by two nitrile N atoms from bridging dca groups, one of the two N atoms of the chelate biq molecule and one nitrile N atom from a terminal dca ligand, whereas the second biq N atom occupies the axial position. Thermal decomposition of1in an air atmosphere proceeds gradually, with copper(I) cyanide being the final decomposition product. Magnetic measurements revealed the formation of alternating spin chains and a relatively strong exchange interaction within the binuclear units was also confirmed by Broken Symmetry DFT (density functional theory) calculations.
Order and disorder in (E)-[1-(biphenyl-4-yl)ethylidene]hydrazine: a structural, spectroscopic and theoretical study
Authors: Tan Xue-Jie , Zhao Qing-Zhe , Li Kun , Hu Yong-Ji , Zhang Jing-Chao
Published: October 2018

An unexpected global disorder (co-existing rotational disorder and glide disorder) has been observed during an X-ray investigation of the crystal structure of (E)-[1-(biphenyl-4-yl)ethylidene]hydrazine, C14H14N2, at room temperature. When the temperature decreases to 273 K, the disorder disappears, but the quality of the data set is low. The diffraction data were collected again at 110 K. Differential scanning calorimetry (DSC) analysis and polarizing-microscopy experiments, as well as a fourth set of single-crystal data collected at 283 K, proved that the order–disorder transformation occurs continuously. The analyses of these crystal structures and full-range relaxed potential energy surface scans showed that this kind of global disorder is not very difficult to achieve inside the crystal. Experimental and theoretical studiesviaUV–Vis and fluorescence spectra impart an understanding on the prediction methods of optical properties, which are essential for the rational design of biphenyl-based materials with pre-defined properties.
Total quality and socially responsible management (TQSR-M)
Authors: Khurshid Muhammad Adnan , Amin Muslim , Ismail Wan Khairuzzaman Wan
Published: October 2018

Purpose

The purpose of this paper is to develop an integrated conceptual framework of total quality management and corporate social responsibility.

Design/methodology/approach

This study is based on stakeholder theory, which stresses the satisfaction of all stakeholders. Therefore, companies generate profit for their shareholders by producing high quality products and services to emphasize human dignity and to satisfy their employees without harming people and the natural environment.

Findings

The results of the study suggest an integrated conceptual framework by identifying the critical factors that are parallel between quality management and social responsibility to satisfy key stakeholders’ demands.

Research limitations/implications

This study is conceptual in nature, and empirical research is needed to identify the critical factors that promote the application of TQM and CSR practices, which are limited.

Practical implications

The proposed conceptual framework may facilitate the management of an organization to evaluate its quality and social programs and will highlight problem areas that can be improved. This study contributes to the literature on TQM and CSR and captures the important factors for effective TQM and CSR practices. The conceptual framework will help researchers and firms to recognize TQM and CSR initiatives and establish a strengthened relationship between corporate strategy and social conditions.

Originality/value

Previous studies have been conducted separately in the areas of TQM and CSR, and there are still not sufficient number of studies to simultaneously integrate quality management and social responsibility. Thus, there is a critical research gap, which raises the question of how the integration of TQM and CSR practices can be developed. There is a need to recognize the mechanism through which the specific element of CSR would be included as an implicit and/or explicit aspect or whether it should be addressed along with TQM. Therefore, this study proposes an integrated conceptual framework that can be applied to the broader issues of responsibility rather than just quality.