bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpersonal behavior in anticipation of pain: a naturalistic study of behavioral mimicry prior to surgery
Authors: Ashton-James Claire E. , Tybur Joshua M. , Forouzanfar Tymour
Published: June 2017

Introduction:

Social relationships facilitate coping with pain, but research suggests that it may be difficult to galvanize social support during an episode of acute pain.

Objectives:

The current research examined whether social connections are optimized in the anticipation of pain by observing patients' mimicry of an interaction partner prior to surgery. We hypothesized that when controlling for their current experience of pain, patients' anticipation of pain would be associated with greater mimicry of an interaction partner.

Methods:

Sixty-five patients were interviewed in the waiting room of a maxillofacial surgery unit prior to the removal of an impacted wisdom tooth. Patients' spontaneous mimicry of an interviewer was observed. Patients then rated the quality and intensity of their anticipated pain, as well as the intensity of their current pain and their affective distress.

Results:

Anticipated pain, current pain, and affective distress were positively correlated. Current pain was associated with less frequent mimicry of an interaction partner. The zero-order correlation between anticipated pain and mimicry did not reach conventional levels of significance; however, when controlling for current pain, anticipated pain predicted more frequent mimicry of an interaction partner. The relationship between anticipated pain and mimicry was not explained by affective distress.

Conclusion:

This is the first study to demonstrate that anticipated and current pain relate to behavioral mimicry in divergent ways. Further research is needed to investigate whether the current pattern of results generalizes to other interpersonal behaviors that facilitate social bonds.
Early Fibrinolysis Associated with Hemorrhagic Progression Following Traumatic Brain Injury
Authors: Karri Jay , Cardenas Jessica C. , Matijevic Nena , Wang Yao-Wei , Choi Sangbum , Zhu Liang , Cotton Bryan A. , Kitagawa Ryan , Holcomb John B. , Wade Charles E.
Published: June 2017

Background:

Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with worse outcomes. PHI pathophysiology remains poorly understood and difficult to predict. We performed an exploratory analysis aimed at identifying markers in need of further investigation to establish their predictive value in PHI following TBI.

Methods:

We performed a retrospective chart review of prospectively collected data from 424 highest-level activation trauma patients from January 2012 through December 2013. Patients with severe TBI, defined as head acute injury scale (AIS) score ≥3 and intracranial hemorrhage (ICH) on initial CT, were included. Stable hemorrhage (SH) and PHI was determined by measuring ICH expansion on repeat CT within 6 h. Of 424 patients evaluated, 72 met inclusion criteria. Twenty-five patients had repeated samples available and were dichotomized into SH (n = 6, 24%) and PHI (n = 19, 76%). Levels of plasminogen, urokinase and tissue plasminogen activators (uPA, tPA), plasminogen activator inhibitor-1, α2-antiplasmin (α2AP), and D-Dimers (DD) were measured upon admission and 2, 4, and 6 h later.

Results:

Longitudinal models identified tPA and DD as positively associated and α2AP inversely associated with PHI. High DD levels are strongly associated with developing PHI over time. Using the full TBI cohort of N = 72, receiver operating curve analysis provided a cutoff of 3.04 μg/mL admission DD to distinguish SH from PHI patients.

Conclusion:

Our findings support a relationship between markers of fibrinolysis in polytrauma patients with severe TBI and PHI, warranting further investigation into the potential for novel, predictive biomarkers.
Role of Hemorrhagic Shock in Experimental Polytrauma
Authors: Denk Stephanie , Weckbach Sebastian , Eisele Philipp , Braun Christian K. , Wiegner Rebecca , Ohmann Julia J. , Wrba Lisa , Hoenes Felix M. , Kellermann Philipp , Radermacher Peter , Wachter Ulrich , Hafner Sebastian , McCook Oscar , Schultze Anke , Palmer Annette , Braumüller Sonja , Gebhard Florian , Huber-Lang Markus
Published: June 2017

Hemorrhagic shock (HS) after tissue trauma increases the complication and mortality rate of polytrauma (PT) patients. Although several murine trauma models have been introduced, there is a lack of knowledge about the exact impact of an additional HS. We hypothesized that HS significantly contributes to organ injury, which can be reliably monitored by detection of specific organ damage markers. Therefore we established a novel clinically relevant PT plus HS model in C57BL/6 mice which were randomly assigned to control, HS, PT, or PT+HS procedure (n = 8 per group). For induction of PT, anesthetized animals received a blunt chest trauma, head injury, femur fracture, and soft tissue injury. HS was induced by pressure-controlled blood drawing (mean arterial blood pressure of 30 mmHg for 60 min) and mice then resuscitated with ionosterile (4 × volume drawn), monitored, and killed for blood and organ harvesting 4 h after injury. After HS and resuscitation, PT+HS mice required earlier and overall more catecholamine support than HS animals to keep their mean arterial blood pressure. HS significantly contributed to the systemic release of interleukin-6 and high mobility group box 1 protein. Furthermore, the histological lung injury score, pulmonary edema, neutrophil influx, and plasma clara cell protein 16 were all significantly enhanced in PT animals in the presence of an additional HS. Although early morphological changes were minor, HS also contributed functionally to remote acute kidney injury but not to early liver damage. Moreover, PT-induced systemic endothelial injury, as determined by plasma syndecan-1 levels, was significantly aggravated by an additional HS. These results indicate that HS adds to the systemic inflammatory reaction early after PT. Within hours after PT, HS seems to aggravate pulmonary damage and to worsen renal and endothelial function which might overall contribute to the development of early multiple organ dysfunction.
Carers and breathlessness
Authors: Farquhar Morag
Published: June 2017

Purpose of review

Informal carers play a key role in supporting patients living with breathlessness in advanced disease, but with considerable impacts on their own well being. The purpose was to review recent advances in our understanding of the caring role in refractory breathlessness, its impacts on carers, and interventions to support them.

Recent findings

A systematic literature search resulted in 28 included articles that could be mapped to four broad areas of carer enquiry: the carer role (n = 6), role impact (n = 7), carer support (n = 11) and carer views (n = 4). Search terms focused on breathlessness, but few of the included articles were exclusively on breathlessness: most were disease-related, predominantly chronic obstructive pulmonary disease (COPD). There were a range of methodologies, including four systematic reviews; UK studies were most common.

Carers of patients with breathlessness take on a role characterized by uncertainty, largely unsupported by healthcare professionals (HCPs). HCP acknowledgement of these carers, their contribution and the impact of the caring role, is lacking. The patient–carer dyad should be considered the unit of care. Carer intervention should be individualized, supporting carers as clients and coworkers. There was a dearth of studies recruiting via primary care, focusing on conditions other than COPD and longitudinal work.
Advanced Neuroimaging Techniques: Basic Principles and Clinical Applications
Authors: Griauzde Julius , Srinivasan Ashok
Published: June 2017

Advanced neuroimaging techniques are increasingly being implemented in clinical practice as complementary tools to conventional imaging because they can provide crucial functional information about the pathophysiology of a variety of disorders. Therefore, it is important to understand the basic principles underlying them and their role in diagnosis and management. In this review, we will primarily focus on the basic principles and clinical applications of perfusion imaging, diffusion imaging, magnetic resonance spectroscopy, functional MRI, and dual-energy computerized tomography. Our goal is to provide the reader with a basic understanding of these imaging techniques and when they should be used in clinical practice.
Short- and Long-term Cognitive Outcomes in Patients With Major Depression Treated With Electroconvulsive Therapy
Authors: Vasavada Megha M. , Leaver Amber M. , Njau Stephanie , Joshi Shantanu H. , Ercoli Linda , Hellemann Gerhard , Narr Katherine L. , Espinoza Randall
Published: June 2017

Objectives

The risk of cognitive impairment is a concern for patients with major depressive disorder receiving electroconvulsive therapy (ECT). Here, we evaluate the acute, short-term and long-term effects of ECT on tests of processing speed, executive function, memory, and attention.

Methods

Forty-four patients with major depressive disorder receiving ECT (61% right unilateral, 39% mixed right unilateral–bitemporal, left unilateral, and/or bitemporal lead placement) underwent a cognitive battery prior to ECT (T1), after 2 sessions (T2), and at the end of the index (T3). Thirty-two patients returned for a 6-month follow-up (T4). Thirty-three control subjects were assessed at 2 times approximately 4 weeks apart (C1 and C2).

Results

At baseline, patients showed deficits in processing speed, executive function, and memory compared with control subjects. Including depression severity and lead placement covariates, linear mixed-model analysis showed significant improvement in only processing speed between T1 and T3 and between T1 and T4 in patients. An acute decline in attention and verbal memory was observed at T2, but performance returned to baseline levels at T3. Longitudinal cognitive outcomes did not differ in patients defined as ECT responders/nonresponders.

Limitations

Episodic memory was not measured, and medications were not controlled between T3 and T4. Control subjects also showed improvements in processing speed, suggesting practice effects for some measures.

Conclusions

In this naturalistic ECT treatment study, results show that the initiation of ECT may transiently affect memory and executive function, but cognition is largely unaffected during and after ECT. Whereas some functions might improve, others will at least remain stable up to 6 months following the ECT index.
The PRIDE Study and the Conduct of Electroconvulsive Therapy
Authors: Rasmussen Keith G.
Published: June 2017

The recently published PRIDE study (prolonging remission in the depressed elderly) constitutes an important contribution to electroconvulsive therapy (ECT) technique, from the standpoint of both the index course to treat depressive symptoms and the post–remission continuation period to prevent relapse. This study was probably the last large, National Institute of Mental Health–funded, multisite ECT technical study for some time to come, so extracting clinically relevant recommendations is worthwhile. In this commentary, the author discusses evidence from this trial relevant to several important clinical index and continuation ECT technical issues and elaborates several unanswered questions deserving further consideration.
Discovery of the fossil otter
Enhydritherium terraenovae
(Carnivora, Mammalia) in Mexico reconciles a palaeozoogeographic mystery
Authors: Tseng Z. Jack , Pacheco-Castro Adolfo , Carranza-Castañeda Oscar , Aranda-Gómez José Jorge , Wang Xiaoming , Troncoso Hilda
Published: June 2017

The North American fossil otter
Enhydritherium terraenovae
is thought to be partially convergent in ecological niche with the living sea otter
Enhydra lutris
, both having low-crowned crushing teeth and a close association with marine environments. Fossil records of
Enhydritherium
are found in mostly marginal marine deposits in California and Florida; despite presence of very rich records of fossil terrestrial mammals in contemporaneous localities inland, no
Enhydritherium
fossils are hitherto known in interior North America. Here we report the first occurrence of
Enhydritherium
outside of Florida and California, in a land-locked terrestrial mammal fauna of the upper Miocene deposits of Juchipila Basin, Zacatecas State, Mexico. This new occurrence of
Enhydritherium
is at least 200 km from the modern Pacific coastline, and nearly 600 km from the Gulf of Mexico. Besides providing further evidence that
Enhydritherium
was not dependent on coastal marine environments as originally interpreted, this discovery leads us to propose a new east-to-west dispersal route between the Florida and California
Enhydritherium
populations through central Mexico. The proximity of the fossil locality to nearby populations of modern neotropical otters
Lontra longicaudis
suggests that trans-Mexican freshwater corridors for vertebrate species in riparian habitats may have persisted for a prolonged period of time, pre-dating the Great American Biotic Interchange.
Regulation of expression of human RNA polymerase II-transcribed snRNA genes
Authors: Guiro Joana , Murphy Shona
Published: June 2017

In addition to protein-coding genes, RNA polymerase II (pol II) transcribes numerous genes for non-coding RNAs, including the small-nuclear (sn)RNA genes. snRNAs are an important class of non-coding RNAs, several of which are involved in pre-mRNA splicing. The molecular mechanisms underlying expression of human pol II-transcribed snRNA genes are less well characterized than for protein-coding genes and there are important differences in expression of these two gene types. Here, we review the DNA features and proteins required for efficient transcription of snRNA genes and co-transcriptional 3′ end formation of the transcripts.
Green approach for synthesis of bioactive Hantzsch 1,4-dihydropyridine derivatives based on thiophene moiety via multicomponent reaction
Authors: Sharma M. G. , Rajani D. P. , Patel H. M.
Published: June 2017

A novel green and efficient one-pot multicomponent reaction of dihydropyridine derivatives was reported as having good to excellent yield. In the presence of the catalyst ceric ammonium nitrate (CAN), different 1,3-diones and same starting materials as 5-bromothiophene-2-carboxaldehyde and ammonium acetate were used at room temperature under solvent-free condition for the Hantzsch pyridine synthesis within a short period of time. All compounds were evaluated for their
in vitro
antibacterial and antifungal activity and, interestingly, we found that
5(b–f)
show excellent activity compared with Ampicillin, whereas only the
5e
compound shows excellent antifungal activity against
Candida albicans
compared with griseofulvin. The cytotoxicity of all compounds has been assessed against breast tumour cell lines (BT-549), but no activity was found. The X-ray structure of one such compound,
5a
, viewed as a colourless block crystal, corresponded accurately to a primitive monoclinic cell.
Taxonomic review of the late Cenozoic megapodes (Galliformes: Megapodiidae) of Australia
Authors: Shute Elen , Prideaux Gavin J. , Worthy Trevor H.
Published: June 2017

Megapodes are unusual galliform birds that use passive heat sources to incubate their eggs. Evolutionary relationships of extant megapode taxa have become clearer with the advent of molecular analyses, but the systematics of large, extinct forms (Progura gallinacea,Progura naracoortensis) from the late Cenozoic of Australia has been a source of confusion. It was recently suggested that the two species ofProgurawere synonymous, and that this taxon dwarfed into the extant malleefowlLeipoa ocellatain the Late Pleistocene. Here, we review previously described fossils along with newly discovered material from several localities, and present a substantial taxonomic revision. We show thatP. gallinaceaandP. naracoortensisare generically distinct, describe two new species of megapode from the Thylacoleo Caves of south-central Australia, and a new genus from Curramulka Quarry in southern Australia. We also show thatL. ocellatawas contemporaneous with larger species. Our phylogenetic analysis places four extinct taxa in a derived clade with the extant Australo-Papuan brush-turkeysTalegalla fuscirostris,L. ocellata,Alectura lathamiandAepypodius bruijnii. Therefore, diversity of brush-turkeys halved during the Quaternary, matching extinction rates of scrubfowl in the Pacific. Unlike extant brush-turkeys, all the extinct taxa appear to have been burrow-nesters.
Occurrence of spintronics behaviour (half-metallicity, spin gapless semiconductor and bipolar magnetic semiconductor) depending on the location of oxygen vacancies in BiFe
0.83
Ni
0.17
O
3
Authors: Rajan P. Iyyappa , Mahalakshmi S. , Chandra Sharat
Published: June 2017

The current communication signifies the effect of oxygen vacancies (OVs) both qualitatively and quantitatively in multiferroic BiFe
0.83
Ni
0.17
O
3
by an in-depth atomic-level investigation of its electronic structure and magnetization properties, and these materials have a variety of applications in spintronics, optoelectronics, sensors and solar energy devices. Depending on the precise location of OVs, all the three types of spintronic material namely half-metallic, spin gapless semiconductor and bipolar magnetic conductor have been established in a single material for the first time and both super-exchange and double-exchange interactions are possible in accordance with the precise location of OVs. We have also calculated the vacancy formation energies to predict their thermodynamic stabilities. These results can highlight the impact and importance of OVs that can alter the multiferroic properties of materials.
A facilitated diffusion model constrained by the probability isotherm: a pedagogical exercise in intuitive non-equilibrium thermodynamics
Authors: Chapman Brian
Published: June 2017

This paper seeks to develop a more thermodynamically sound pedagogy for students of biological transport than is currently available from either of the competing schools of linear non-equilibrium thermodynamics (LNET) or Michaelis–Menten kinetics (MMK). To this end, a minimal model of facilitated diffusion was constructed comprising four reversible steps:cis-substrate binding,cis→transbound enzyme shuttling,trans-substrate dissociation andtrans→cisfree enzyme shuttling. All model parameters were subject to the second law constraint of the probability isotherm, which determined the unidirectional and net rates for each step and for the overall reaction through the law of mass action. Rapid equilibration scenarios require sensitive ‘tuning’ of the thermodynamic binding parameters to the equilibrium substrate concentration. All non-equilibrium scenarios show sigmoidal force–flux relations, with only a minority of cases having theirquasi-linear portions close to equilibrium. Few cases fulfil the expectations of MMK relating reaction rates to enzyme saturation. This new approach illuminates and extends the concept of rate-limiting steps by focusing on the free energy dissipation associated with each reaction step and thereby deducing its respective relative chemical impedance. The crucial importance of an enzyme's being thermodynamically ‘tuned’ to its particular task, dependent on thecis-andtrans-substrate concentrations with which it deals, is consistent with the occurrence of numerous isoforms for enzymes that transport a given substrate in physiologically different circumstances. This approach to kinetic modelling, being aligned with neither MMK nor LNET, is best described as intuitive non-equilibrium thermodynamics, and is recommended as a useful adjunct to the design and interpretation of experiments in biotransport.
Nonlinear model identification and spectral submanifolds for multi-degree-of-freedom mechanical vibrations
Authors: Szalai Robert , Ehrhardt David , Haller George
Published: June 2017

In a nonlinear oscillatory system, spectral submanifolds (SSMs) are the smoothest invariant manifolds tangent to linear modal subspaces of an equilibrium. Amplitude–frequency plots of the dynamics on SSMs provide the classic backbone curves sought in experimental nonlinear model identification. We develop here, a methodology to compute analytically both the shape of SSMs and their corresponding backbone curves from a data-assimilating model fitted to experimental vibration signals. This model identification utilizes Taken’s delay-embedding theorem, as well as a least square fit to the Taylor expansion of the sampling map associated with that embedding. The SSMs are then constructed for the sampling map using the parametrization method for invariant manifolds, which assumes that the manifold is an embedding of, rather than a graph over, a spectral subspace. Using examples of both synthetic and real experimental data, we demonstrate that this approach reproduces backbone curves with high accuracy.
Windowed Green function method for the Helmholtz equation in the presence of multiply layered media
Authors: Bruno O. P. , Pérez-Arancibia C.
Published: June 2017

This paper presents a new methodology for the solution of problems of two- and three-dimensional acoustic scattering (and, in particular, two-dimensional electromagnetic scattering) by obstacles and defects in the presence of an arbitrary number of penetrable layers. Relying on the use of certain slow-rise windowing functions, the proposed windowed Green function approach efficiently evaluates oscillatory integrals over unbounded domains, with high accuracy, without recourse to the highly expensive Sommerfeld integrals that have typically been used to account for the effect of underlying planar multilayer structures. The proposed methodology, whose theoretical basis was presented in the recent contribution (Bruno
et al.
2016
SIAM J. Appl. Math.
76
, 1871–1898. (
doi:10.1137/15M1033782
)), is fast, accurate, flexible and easy to implement. Our numerical experiments demonstrate that the numerical errors resulting from the proposed approach decrease faster than any negative power of the window size. In a number of examples considered in this paper, the proposed method is up to thousands of times faster, for a given accuracy, than corresponding methods based on the use of Sommerfeld integrals.
The importance of individual and species-level traits for trophic niches among herbivorous coral reef fishes
Authors: Allgeier Jacob E. , Adam Thomas C. , Burkepile Deron E.
Published: June 2017

Resolving how species compete and coexist within ecological communities represents a long-standing challenge in ecology. Research efforts have focused on two predominant mechanisms of species coexistence: complementarity and redundancy. But findings also support an alternative hypothesis that within-species variation may be critical for coexistence. Our study focuses on nine closely related and ecologically similar coral reef fish species to test the importance of individual- versus species-level traits in determining the size of dietary, foraging substrate, and behavioural interaction niches. Specifically, we asked: (i) what level of biological organization best describes individual-level niches? and (ii) how are herbivore community niches partitioned among species, and are niche widths driven by species- or individual-level traits? Dietary and foraging substrate niche widths were best described by species identity, but no level of taxonomy explained behavioural interactions. All three niches were dominated by only a few species, contrasting expectations of niche complementarity. Species- and individual-level traits strongly drove foraging substrate and behavioural niches, respectively, whereas the dietary niche was described by both. Our findings underscored the importance of species-level traits for community-level niches, but highlight that individual-level trait variation within a select few species may be a key driver of the overall size of niches.
Evolvability meets biogeography: evolutionary potential decreases at high and low environmental favourability
Authors: Martínez-Padilla J. , Estrada A. , Early R. , Garcia-Gonzalez F.
Published: June 2017

Understanding and forecasting the effects of environmental change on wild populations requires knowledge on a critical question: do populations have the ability to evolve in response to that change? However, our knowledge on how evolution works in wild conditions under different environmental circumstances is extremely limited. We investigated how environmental variation influences the evolutionary potential of phenotypic traits. We used published data to collect or calculate 135 estimates of evolvability of morphological traits of European wild bird populations. We characterized the environmental favourability of each population throughout the species' breeding distribution. Our results suggest that the evolutionary potential of morphological traits decreases as environmental favourability becomes high or low. Strong environmental selection pressures and high intra-specific competition may reduce species' evolutionary potential in low- and high- favourability areas, respectively. This suggests that species may be least able to adapt to new climate conditions at their range margins and at the centre. Our results underscore the need to consider the evolutionary potential of populations when studying the drivers of species distributions, particularly when predicting the effects of environmental change. We discuss the utility of integrating evolutionary dynamics into a biogeographical perspective to understand how environmental variation shapes evolutionary patterns. This approach would also produce more reliable predictions about the effect of environmental change on population persistence and therefore on biodiversity.
X-ray micro-CT scanning reveals temporal separation of male harm and female kicking during traumatic mating in seed beetles
Authors: Dougherty Liam R. , Simmons Leigh W.
Published: June 2017

In the seed beetle
Callosobruchus maculatus
, the male intromittent organ is covered in sharp spines that pierce the female copulatory tract wall during mating. Although the fitness consequences of traumatic mating are well studied in this species, we know much less about how the male and female genitalia interact during mating. This is partly due to the fact that genital interactions occur primarily inside the female, and so are difficult to observe. In this study, we use X-ray micro-CT scanning to examine the proximate mechanisms of traumatic mating in
C. maculatus
in unprecedented detail. We show that this technique can be used to identify female tissue damage before the melanization of wound sites. We visualize the positioning of the male intromittent organ inside the female copulatory tract during mating, and show how this relates to tract wounding in three dimensions. By scanning pairs flash-frozen at different times during mating, we show that significant tract wounding occurs before the onset of female kicking. There is thus some degree of temporal separation between the onset of wounding and the onset of kicking, which supports recent suggestions that kicking is not an effective female counter-adaptation to reduce copulatory wounding in this species. We also present evidence that the sharp teeth protruding from the female tract wall are able to pierce the spermatophore as it is deposited, and may thus function to aid sperm release.
Phylogenomics and comparative genomics of Lactobacillus salivarius, a mammalian gut commensal
Authors: Harris Hugh M.B. , Bourin Maxence J. B. , Claesson Marcus J. , O'Toole Paul W.
Published: June 2017

The genus Lactobacillus is a diverse group with a combined species count of over 200. They are the largest group within the lactic acid bacteria and one of the most important bacterial groups involved in food microbiology and human nutrition because of their fermentative and probiotic properties. Lactobacillus salivarius, a species commonly isolated from the gastrointestinal tract of humans and animals, has been described as having potential probiotic properties and results of previous studies have revealed considerable functional diversity existing on both the chromosomes and plasmids. Our study consists of comparative genomic analyses of the functional and phylogenomic diversity of 42 genomes of strains of L
. salivarius using bioinformatic techniques. The main aim of the study was to describe intra-species diversity and to determine how this diversity is spread across the replicons. We found that multiple phylogenomic and non-phylogenomic methods used for reconstructing trees all converge on similar tree topologies, showing that different metrics largely agree on the evolutionary history of the species. The greatest genomic variation lies on the small plasmids, followed by the repA-type circular megaplasmid, with the chromosome varying least of all. Additionally, the presence of extra linear and circular megaplasmids is noted in several strains, while small plasmids are not always present. Glycosyl hydrolases, bacteriocins and proteases vary considerably on all replicons while two exopolysaccharide clusters and several clustered regularly interspaced short palindromic repeats-associated systems show a lot of variation on the chromosome. Overall, despite its reputation as a mammalian gastrointestinal tract specialist, the intra-specific variation of L. salivarius reveals potential strain-dependant effects on human health.
Mutational signatures of DNA mismatch repair deficiency inC. elegansand human cancers
Authors: Meier B , Volkova NV , Hong Y , Schofield P , Campbell PJ , Gerstung M , Gartner A
Published: June 2017

Throughout their lifetime cells are subject to extrinsic and intrinsic mutational processes leaving behind characteristic signatures in the genome. DNA mismatch repair (MMR) deficiency leads to hypermutation and is found in different cancer types. While it is possible to associate mutational signatures extracted from human cancers with possible mutational processes the exact causation is often unknown. Here we useC. elegansgenome sequencing ofpms-2andmlh-1knockouts to reveal the mutational patterns linked toC. elegansMMR deficiency and their dependency on endogenous replication errors and errors caused by deletion of the polymerase ε subunitpole-4. Signature extraction from 215 human colorectal and 289 gastric adenocarcinomas revealed three MMR-associated signatures, one of which closely resembles theC. elegansMMR spectrum and strongly discriminates microsatellite stable and unstable tumors (AUC=98%). A characteristic difference between human andC. elegansMMR deficiency is the lack of elevated levels of NCG>NTG mutations inC. elegans, likely caused by the absence of cytosine (CpG) methylation in worms. The other two human MMR signatures may reflect the interaction between MMR deficiency and other mutagenic processes, but their exact cause remains unknown. In summary, combining information from genetically defined models and cancer samples allows for better aligning mutational signatures to causal mutagenic processes.
Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the earlyDrosophila melanogasterembryo
Authors: Stadler Michael R. , Haines Jenna E. , Eisen Michael B.
Published: June 2017

Evidence has emerged in recent years linking insulators and the proteins that bind them to the higher order structure of animal chromatin, but the precise nature of this relationship and the manner by which insulators influence chromatin structure have remained elusive. Here we present high-resolution genome-wide chromatin conformation capture (Hi-C) data from earlyDrosophila melanogasterembryos that allow us to map three-dimensional interactions to 500 base pairs. We observe a complex, nested pattern of regions of chromatin self-association, and use a combination of computational and manual annotation to identify boundaries between these topological associated domains (TADs). We demonstrate that, when mapped at high resolution, boundaries resemble classical insulators: short (500 - 1000 bp) genomic regions that are sensitive to DNase digestion and strongly bound by known insulator proteins. Strikingly, we show that for regions where the banding pattern of polytene chromosomes has been mapped to genomic position at comparably high resolution, there is a perfect correspondence between polytene banding and our chromatin conformation maps, with boundary insulators forming the interband regions that separate compacted bands that correspond to TADs. We propose that this precise, high-resolution relationship between insulators and TADs on the one hand and polytene bands and interbands on the other extends across the genome, and suggest a model in which the decompaction of insulator regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains.
A functional role for the epigenetic regulator ING1 in activity-induced gene expression in primary cortical neurons
Authors: Leighton Laura J. , Zhao Qiongyi , Li Xiang , Dai Chuanyang , Marshall Paul R. , Liu Sha , Wang Yi , Zajaczkowski Esmi L. , Khandelwal Nitin , Kumar Arvind , Bredy Timothy W. , Wei Wei
Published: June 2017

Epigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of Inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin,Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) ofPpp3r1depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair.

Author contributions

L.J.L., Q.Z., T.W.B and W.W. designed the experiments. N.K., A.K., X.L., C.D., S.L. and W.W. designed and assembled shRNA constructs. L.J.L., W.W., X.L., C.D., P.R.M., E.Z., and S.L. conducted experiments. Q.Z. and Y.W. analysed ChIP-seq data. L.J.L., Q.Z., and W.W. wrote the paper. All authors reviewed and edited the manuscript.

Conflicts of interest

None.
Oxytocin gene networks in the human brain: A gene expression and large-scale fMRI meta-analysis study
Authors: Quintana Daniel S. , Rokicki Jaroslav , van der Meer Dennis , Alnæs Dag , Kaufmann Tobias , Palomera Aldo Córdova , Dieset Ingrid , Andreassen Ole A. , Westlye Lars T.
Published: June 2017

Oxytocin is a neuropeptide involved in animal and human reproductive and social behavior, with implications for a range of psychiatric disorders. However, the therapeutic potential of oxytocin in mental health care suggested by animal research has not been successfully translated into clinical practice. This may be partly due to a poor understanding of the expression and distribution of the oxytocin signaling pathway in the human brain, and its complex interactions with other biological systems. Among the genes involved in the oxytocin signaling pathway, three genes have been frequently implicated in human social behavior:OXT(structural gene for oxytocin),OXTR(oxytocin receptor), andCD38(central oxytocin secretion). We characterized the distribution ofOXT, OXTR,andCD38mRNA across the brain, identified putative gene pathway interactions by comparing gene expression patterns across 20737 genes, and assessed associations between gene expression patterns and mental states via large-scale fMRI metaanalysis. In line with the animal literature, expression of the three selected oxytocin pathway genes was increased in central, temporal, and olfactory regions. Across the brain, there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. Finally, fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with motivation and emotion processing.
Beyond Consensus: Embracing Heterogeneity in Curated Neuroimaging Meta-Analysis
Authors: Ngo Gia H. , Eickhoff Simon B. , Nguyen Minh , Sevinc Gunes , Fox Peter T. , Spreng R. Nathan , Thomas Yeo B.T.
Published: June 2017

Coordinate-based meta-analysis can provide important insights into mind-brain relationships. A popular approach for curated small-scale meta-analysis is activation likelihood estimation (ALE), which identifies brain regions consistently activated across a selected set of experiments, such as within a functional domain or mental disorder. ALE can also be utilized in meta-analytic co-activation modeling (MACM) to identify brain regions consistently co-activated with a seed region. Therefore, ALE aims to find consensus across experiments, treating heterogeneity across experiments as noise. However, heterogeneity within an ALE analysis of a functional domain might indicate the presence of functional sub-domains. Similarly, heterogeneity within a MACM analysis might indicate the involvement of a seed region in multiple co-activation patterns that are dependent on task contexts. Here, we demonstrate the use of the author-topic model to automatically determine if heterogeneities within ALE-type meta-analyses can be robustly explained by a small number of latent patterns. In the first application, the author-topic modeling of experiments involving self-generated thought (N = 179) revealed cognitive components fractionating the default network. In the second application, the author-topic model revealed that the left inferior frontal junction (IFJ) participated in multiple task-dependent co-activation patterns (N = 323). Furthermore, the author-topic model estimates compared favorably with spatial independent component analysis in both simulation and real data. Overall, the results suggest that the author-topic model is a flexible tool for exploring heterogeneity in ALE-type meta-analyses that might arise from functional sub-domains, mental disorder subtypes or task-dependent co-activation patterns. Code for this study is publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/meta-analysis/Ngo2019_AuthorTopic).
tDCS changes in motor excitability are specific to orientation of current flow
Authors: Rawiji Vishal , Ciocca Matteo , Zacharia André , Soares David , Truong Dennis , Bikson Marom , Rothwell John , Bestmann Sven
Published: June 2017

Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the cephalic cortex result in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. Here we test this idea by measuring changes in cortico-spinal excitability by Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP), following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. Current flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces none-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is through to select different afferent pathways to M1. Our results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.

Highlights

Direction of current flow is important for tDCS after-effects.

tDCS modulates excitability between two electrodes.

tDCS differentially modulates PA and AP inputs into M1.

Abbreviations

PA

postero-anterior

AP

antero-posterior

ML

medio-lateral

tDCS

transcranial direct current stimulation

MEP

motor evoked potential

M1

primary motor cortex

TMS

transcranial magnetic stimulation;

AP-TMS-MEPs

motor evoked potentials elicited with anterior-posterior directed TMS;

PA-TMS-MEPs

motor evoked potentials elicited with posterior-anterior directed TMS

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors
Authors: Olson William , Abdus-Saboor Ishmail , Cui Lian , Burdge Justin , Raabe Tobias , Ma Minghong , Luo Wenqin
Published: June 2017

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying the ‘pain fovea’, we sparsely traced non-peptidergic nociceptors across the body using a newly generatedMrgprDCreERT2mouse line. We found that mouse plantar paw skin also has a low density of MrgprD+neurites, and individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the magnification of plantar paw regions to contribute to the ‘pain fovea’.
Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells
Authors: Gonçalves Emanuel , Sciacovelli Marco , Costa Ana S. H. , Isaac Johnson Timothy , Machado Daniel , Frezza Christian , Saez-Rodriguez Julio
Published: June 2017

Deregulated signal transduction pathways and energy metabolism are hallmarks of cancer and both play a fundamental role in the process of tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we show that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers.
Pattern decomposition for residual stress analysis: a generalization taking into consideration elastic anisotropy and extension to higher-symmetry Laue classes
Authors: Schoderböck Peter , Leibenguth Peter , Tkadletz Michael
Published: June 2017

The residual stress state of ion-conducting layers (yttria stabilized zirconia) and protective hard coatings (α-aluminium oxide, titanium carbonitride) was investigated using X-ray diffraction techniques. Its evaluation within the tetragonal, trigonal and cubic phases present was performed by a whole powder pattern decomposition procedure according to Pawley. Going beyond previous work, the applied refinements directly include the influence of elastic anisotropy on the residual stress results. Starting from the single-crystal elastic coefficients, the X-ray elastic constants according to the Voigt and Reuss models were calculated. Finally, the Neerfeld–Hill model as a generalization was implemented to introduce thehkl-specific X-ray elastic constants for calculating the residual stress magnitude within the least-squares minimization routine. It was possible to resolve the residual stress state in stacked layers of different chemical and phase composition and to reproduce the results obtained by the classical χ- and ω-inclination sin2Ψ techniques.
Normal tracing deflectometry using a secondary light source
Authors: Peng Chuanqian , He Yumei , Wang Jie
Published: June 2017

Scanning deflectometric profilers based on an f–θ system are typical optical tools used to measure mirror profiles at many synchrotron facilities. Unlike these profilers, which are based on a pencil beam, here a secondary light source and a pinhole are used to construct a system that automatically selects a beam that will always pass through the pinhole and propagate along the normal direction of the measured area on the surface under test. By measuring the angle variation of the selected beam, slope variations of the surface under test can be measured. Systematic errors introduced by manufacturing defects or aberrations of an optical element, which greatly degrade the performance of traditional profilers, could be minimized by using the developed method. Simulation values of the proposed method and a conventional method are compared.
Making crystals with a purpose; a journey in crystal engineering at the University of Bologna
Authors: Braga Dario , Grepioni Fabrizia , Maini Lucia , d'Agostino Simone
Published: June 2017

The conceptual relationship between crystal reactivity, stability and metastability, solubility and morphology on the one hand and shape, charge distribution, chirality and distribution of functional groups over the molecular surfaces on the other hand is discussed,viaa number of examples coming from three decades of research in the field of crystal engineering at the University of Bologna. The bottom-up preparation of mixed crystals, co-crystals and photoreactive materials starting from molecular building blocks across the borders of organic, organometallic and metalorganic chemistry is recounted.
Classification of crystal structure using a convolutional neural network
Authors: Park Woon Bae , Chung Jiyong , Jung Jaeyoung , Sohn Keemin , Singh Satendra Pal , Pyo Myoungho , Shin Namsoo , Sohn Kee-Sun
Published: June 2017

A deep machine-learning technique based on a convolutional neural network (CNN) is introduced. It has been used for the classification of powder X-ray diffraction (XRD) patterns in terms of crystal system, extinction group and space group. About 150 000 powder XRD patterns were collected and used as input for the CNN with no handcrafted engineering involved, and thereby an appropriate CNN architecture was obtained that allowed determination of the crystal system, extinction group and space group. In sharp contrast with the traditional use of powder XRD pattern analysis, the CNN never treats powder XRD patterns as a deconvoluted and discrete peak position or as intensity data, but instead the XRD patterns are regarded as nothing but a pattern similar to a picture. The CNN interprets features that humans cannot recognize in a powder XRD pattern. As a result, accuracy levels of 81.14, 83.83 and 94.99% were achieved for the space-group, extinction-group and crystal-system classifications, respectively. The well trained CNN was then used for symmetry identification of unknown novel inorganic compounds.