bluuebunny/crossref_metadata_2025 huggingface dataset:
Underlying Chronic Disease, Medication Use, History of Running Injuries and Being a More Experienced Runner Are Independent Factors Associated With Exercise-Associated Muscle Cramping: A Cross-Sectional Study in 15778 Distance Runners
Authors: Schwellnus Martin P. , Swanevelder Sonja , Jordaan Esme , Derman Wayne , Van Rensburg Dina C. Janse
Published: September 2017

Background:

Exercise-associated muscle cramping (EAMC) is a significant medical complication in distance runners, yet factors associated with EAMC are poorly documented.

Objective:

To document risk factors associated with EAMC in runners.

Design:

Cross-sectional study.

Setting:

Two ocean races (21.1 km, and 56 km).

Participants:

Fifteen thousand seven hundred seventy-eight race entrants.

Methods:

Participants completed a prerace medical history screening tool including: training, cardiovascular disease (CVD), risk factors for, and symptoms of CVD, history of diseases affecting major organ systems, cancer, allergies, medication use, and running injury. Runners were grouped as having a history of EAMC (hEAMC group = 2997) and a control group (Control = 12 781).

Results:

Independent factors associated with a higher prevalence ratio (PR) of hEAMC were any risk factor for CVD (PR = 1.16; P = 0.0002), symptoms of CVD (PR = 2.38; P < 0.0001), respiratory disease (PR = 1.33; P < 0.0001), gastrointestinal disease (PR = 1.86; P < 0.0001), nervous system or psychiatric disease (PR = 1.51; P < 0.0001), kidney or bladder disease, (PR = 1.60; P < 0.0001), haematological or immune disease (PR = 1.54; P = 0.0048), cancer (PR = 1.34; P = 0.0031), allergies (PR = 1.37; P < 0.0001), regular medication use (PR = 1.80; P < 0.0001), statin use (PR = 1.26; P = 0.0127), medication use during racing (PR = 1.88; P < 0.0001), running injury (PR = 1.66; P < 0.0001), muscle injury (PR = 1.82; P < 0.0001), tendon injury (PR = 1.62; P < 0.0001), and runners in the experienced category (PR = 1.22; P < 0.0001).

Conclusion:

Novel risk factors associated with EAMC in distance runners were underlying chronic disease, medication use, a history of running injuries, and experienced runners. These factors must be identified as possible associations, and therefore be considered in the diagnosis and treatment of EAMC.
Children and Adolescent Hodgkin Lymphoma in Argentina: Long-term Results After Combined ABVD and Restricted Radiotherapy
Authors: Zubizarreta Pedro A. , Alfaro Elizabeth , Guitter Myriam , Sanchez La Rosa Cristian , Galluzzo María L. , Millán Natalia , Fiandrino Fernando , Felice María S.
Published: September 2017

Objective:

Prospective analysis of clinical characteristics and long-term treatment results of a pediatric cohort with Hodgkin lymphoma (HL) treated in a single institution with ABVD and restricted radiotherapy (RT).

Patients and Methods:

Between September 2000 and December 2015, 165 new consecutive assessable patients with HL were registered at our institution. Lymphocyte predominant nodular HL was excluded. Low risk (LR) patients were stage I and IIA (no bulky disease, <4 involved ganglionar areas and no lung hilar nodes), high risk (HR) was assigned to stage IV and any other stage with bulky mediastinum. The rest of the cohort was treated as intermediate risk (IR). Chemotherapy for LR and IR patients was 4 and 6 courses of ABVD regimen, respectively. These subsets received Low-dose involved field radiotherapy only in case of partial remission at the end of chemotherapy (21 Gy in initially involved areas, plus 14 Gy boost on residual disease). The HR group was treated with 6 courses of ABVD followed always with 21 Gy involved field radiotherapy if complete remission (CR) was achieved. A boost of 14 Gy was added to residual disease in case of partial remission.

Results:

Median age was 10.6 years (range, 2.7 to 17 y). Males: 117 (71%); females: 48 (29%). Eighteen (11%) patients were stage I, 76 (46%) stage II, 35 (21%) stage III, and 35 (21%) stage IV. Forty-nine (30%) patients were assigned to LR, 49 (30%) to IR, and 67 (40%) to HR. Forty-three patients (26%) had “bulky” mediastinum involvement. One hundred thirty (79%) patients achieved CR after chemotherapy and 161 (98%) after RT. Four patients (all HR), did not respond to initial therapy and died of disease. One patient died in first CR due to adenovirus infection on previously therapy-related damaged lungs. Seventeen (10%) patients relapsed and 13 of them remained in second CR after further therapy. Seventy-six (46%) patients could be spared from RT and cured of disease (88% of LR patients and 67% of IR patients). With a median follow-up of 5 years, event free and overall survival were 0.84 (SE: 0.03) and 0.95 (SE: 0.02), respectively. Overall survival according to risk group was 1 for LR, 0.93 for IR, and 0.85 for HR. Acute toxicity and late effects due to therapy were not significant.

Conclusions:

The strategy of avoiding RT for LR and IR patients that responded completely to ABVD chemotherapy achieved very good results. For the HR group, the combination of 6 cycles of ABVD and Low-dose involved field radiotherapy was efficacious with similar good results. Nearly half of the patients could be cured without RT.
Therapy-related Acute Leukemia With Mixed Phenotype and Novel t(1:6)(q25;p23) After Treatment for High-risk Neuroblastoma
Authors: Whittle Sarah B. , Punia Jyotinder N. , López-Terrada Dolores , Gaikwad Amos , Hampton Oliver A. , Heczey Andras
Published: September 2017

Neuroblastoma is the most common extracranial malignancy of childhood. Patients with high-risk disease receive multimodal treatment including chemotherapy combinations containing alkylating agents and topoisomerase inhibitors with potential for inducing therapy-related malignancy later in life. Most commonly, cytogenetic changes of pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia involve chromosome 5 or 7. Here we report a novel case of therapy-related myelodysplastic syndrome/acute myeloid leukemia 30 months after treatment for high-risk neuroblastoma with biphenotypic cell surface markers and a not yet described translocation t(1;6)(q25;p23).
Factors Affecting Suicide Method Lethality Among Suicide Attempters in the Korea National Suicide Survey
Authors: Yeum Tae-Sung , Kim Bora , Kim Eun Young , Kim Se Hyun , Ha Kyooseob , Ahn Yong Min
Published: September 2017

This is the first national survey study in South Korea investigating the relationship between suicide lethality and the clinical information of suicide attempters. An interview questionnaire was used to assess their sociodemographic factors, medical and psychiatric information, and two suicide scales, the Columbia–Suicide Severity Rating Scale and the Suicide Intent Scale. Suicide methods were categorized as low and high lethality; low lethality covered drug overdose or self-cutting behavior, and high lethality covered all other methods. High and low lethality suicide method groups were significantly different in demographic, medical, and psychiatric factors. The two scale score distributions differed significantly across two groups, and the difference was also valid for the subcategory analyses of the Suicide Intent Scale. Multiple factors such as older age, male sex, no previous psychiatric history, and previous suicide attempt, as well as high suicide intent by means of suicide scale, affect selection of suicide method of high lethality.
Dentoalveolar Effects of Early Orthodontic Treatment in Patients With Cleft Lip and Palate
Authors: Cassi Diana , Di Blasio Alberto , Gandolfinini Mauro , Magnifico Marisabel , Pellegrino Francesca , Piancino Maria Grazia
Published: September 2017

No agreement exists on the most appropriate timing of orthodontic treatment in patients with cleft lip and palate. The aim of this study is to investigate the effect of early orthodontic treatment on development of the dental arches and alveolar bone.

A dental casts analysis was performed on 28 children with cleft lip and palate before orthodontic treatment (T0; mean age, 6.5 ± 1.7) and at the end of active treatment (T1; mean age, 9.2 ± 2.1 years). The considered variables were: intercanine and intermolar distances; dental arch relationships, evaluated according to the modified Huddart/Bodenham system.

The study group was divided into 2 samples according to the age at T0: Group A (age < 6 years) and Group B (age ≥ 6 years). A statistical comparison of the treatment effects between the 2 samples was performed.

Patients in Group A exhibited a greater increase of intercanine distance (8 mm versus 2.7 mm; P<0.001), intermolar distance (7.2 mm versus 5 mm; P = 0.06), and Huddart/Bodenham score (7.1 versus 3; P < 0.05) when compared with patients in Group B.

Early orthodontic treatment strongly improved the dental arch relationship, since subjects starting the therapy before the age of 6 had a better response in terms of anterior maxillary expansion.
Vascular Anomalies of Posterior Fossa and Their Implications
Authors: Singh Rajani , Kumar Raj , Kumar Arushi
Published: September 2017

Posterior fossa houses very vital and sensitive structures namely midbrain, pons, medulla, and cerebellum. These structures are irrigated by vertebral, posterior inferior cerebellar, anterior inferior cerebellar, and superior cerebellar arteries. Parts of brain located in posterior fossa control important parts of body so any variation pertaining to stenosis, atresia, hypoplasia, fenestration, agenesis, and duplication in the arteries supplying these parts alter the irrigation pattern culminating into various morbid and mortal neurologic disorders. Therefore, a sound understanding and thorough knowledge of posterior circulation vascular variant anatomy builds the foundation for the accurate diagnosis and appropriate management of neurovascular ischemic and hemorrhagic diseases of posterior fossa. To aid in addressing these complex neurologic disorders and neurosurgical treatment to be carried out successfully, updating and consolidating the knowledge of all the variations/insults of these arteries becomes essential. Therefore, review study has been carried out.

Literature search was carried out using databases, including Scielo, Scopmed, Medline, PubMed, and Wiley online library. Papers containing original data were selected and secondary references retrieved from bibliographies. Search terms used were posterior fossa, anomalies of vertebral, posterior inferior cerebellar, anterior inferior cerebellar, and superior cerebellar arteries.

The study will be of paramount importance to angiographers in interpreting angiographs, neurologists in diagnosis and treatment of neurologic disorders, and neurosurgeons in performing surgery in posterior fossa and craniovertebral region particularly dealing with tumors and vascular malformations.
Maxillary Hypoplasia: Differential Diagnosis of Nasal Obstruction in Infants
Authors: da Costa Amanda Lucas , Manica Denise , Manzini Michelle , Bernardi Andressa , Pérez Juliano Adams , Sekine Leo , Collares Marcus Vinicius Martins , Kuhl Gabriel , Schweiger Claudia
Published: September 2017

Maxillary hypoplasia (MH) is a rare cause of respiratory dysfunction in infants and may occur in association with genetic abnormalities or as an isolated condition. It is included in the differential diagnosis of congenital nasal obstruction. This paper seeks to report a case series of infants with MH, discuss methods for its diagnosis, and compare computed tomography (CT) measurements of nasal cavities of infants with MH and without craniomaxillofacial abnormalities. The therapeutic approach in each patient is also described. All infants with MH admitted to a tertiary hospital between 2012 and 2015 were included. Baseline nasal endoscopy was performed at bedside. The width of the infants’ nasal cavities was measured by a radiologist with experience in CT scanning of facial bones. Control patients were infants of matched sex and similar age who underwent head CT scanning for various reasons. Overall, 8 infants with MH and 8 controls were assessed. All nasal cavity dimensions of infants with MH were significantly smaller than those of control subjects. The authors conclude that the diagnosis of MH should be considered in infants with nasal obstruction and nasal cavity narrowing at nasal endoscopy.
Alpha oscillations control cortical gain by modulating excitatory-inhibitory background activity
Authors: Peterson Erik J. , Voytek Bradley
Published: September 2017

The first recordings of human brain activity in 1929 revealed a striking 8-12 Hz oscillation in the visual cortex. During the intervening 90 years, these alpha oscillations have been linked to numerous physiological and cognitive processes. However, because of the vast and seemingly contradictory cognitive and physiological processes to which it has been related, the physiological function of alpha remains unclear. We identify a novel neural circuit mechanism—the modulation of both excitatory and inhibitory neurons in abalancedconfiguration—by which alpha can modulate gain. We find that this model naturally unifies the prior, highly diverse reports on alpha dynamics, while making the novel prediction that alpha rhythms have two functional roles: a sustained high-power mode that suppresses scortical gain and a weak, bursting mode that enhances gain.
Cueing memory during sleep is optimal during slow-oscillatory up-states
Authors: Göldi Maurice , van Poppel Eva , Rasch Björn , Schreiner Thomas
Published: September 2017

Slow oscillations play a major role in neural plasticity. It is assumed that slow oscillatory up-states represent crucial time windows for memory reactivation and consolidation during sleep. Here we experimentally tested this assumption by utilizing closed-loop targeted memory reactivation (closed-loop TMR): Healthy participants were re-exposed to prior learned foreign vocabulary during up- and down-states of slow oscillations, respectively, in a within-subject design. We show that presenting memory cues during slow oscillatory up-states robustly improves recall performance, whereas memory cueing during down-states did not result in a clear behavioral benefit. On a neural basis successful memory reactivation during up-states was associated with a characteristic power increase in the theta and sleep spindle band. Such increases were completely absent for down-state memory cues. Our findings provide experimental support for the assumption that slow oscillatory up-states represent privileged time windows for memory reactivation, while the interplay of slow oscillations, theta and sleep spindle activity promote successful memory consolidation during sleep.
Trendy: Segmented regression analysis of expression dynamics for high-throughput ordered profiling experiments
Authors: Bacher Rhonda , Leng Ning , Chu Li-Fang , Thomson James , Kendziorski Christina , Stewart Ron
Published: September 2017

Abstract

High throughput expression profiling experiments with ordered conditions (e.g. time-course or spatial-course) are becoming more common for profiling detailed differentiation processes or spatial patterns. Identifying dynamic changes at both the individual gene and whole transcriptome level can provide important insights about genes, pathways, and critical time-points. We present an R package,Trendy, which utilizes segmented regression models to simultaneously characterize each gene’s expression pattern and summarize overall dynamic activity in ordered condition experiments. For each gene, Trendy finds the optimal segmented regression model and provides the location and direction of dynamic changes in expression. We demonstrate the utility of Trendy to provide biologically relevant results on both microarray and RNA-seq datasets. Trendy is a flexible R package which characterizes gene-specific expression patterns and summarizes changes of global dynamics over ordered conditions. Trendy is freely available as an R package with a full vignette athttps://github.com/rhondabacher/Trendy.
Paratope Prediction using Convolutional and Recurrent Neural Networks
Authors: Liberis Edgar , Veličković Petar , Sormanni Pietro , Vendruscolo Michele , Liò Pietro
Published: September 2017

Antibodies play an essential role in the immune system of vertebrates and are vital tools in research and diagnostics. While hypervariable regions of antibodies, which are responsible for binding, can be readily identified from their amino acid sequence, it remains challenging to accurately pinpoint which amino acids will be in contact with the antigen (the paratope). In this work, we present a sequence-based probabilistic machine learning algorithm for paratope prediction, named Parapred. Parapred uses a deep-learning architecture to leverage features from both local residue neighbourhoods and across the entire sequence. The method outperforms the current state-of-the-art methodology, and only requires a stretch of amino acid sequence corresponding to a hypervariable region as an input, without any information about the antigen. We further show that our predictions can be used to improve both speed and accuracy of a rigid docking algorithm. The Parapred method is freely available athttps://github.com/eliberis/parapredfor download.
Impeding transcription of expanded microsatellite repeats by deactivated Cas9
Authors: Pinto Belinda S. , Saxena Tanvi , Oliveira Ruan , Méndez-Gómez Héctor R. , Cleary John D. , Denes Lance T. , McConnell Ona , Arboleda Juan , Xia Guangbin , Swanson Maurice S. , Wang Eric T.
Published: September 2017

Transcription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs’ endothelial corneal dystrophy, andC9orf72-ALS/FTD. Eliminating or reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that a deactivated form of the Cas9 enzyme impedes transcription across expanded microsatellites. We observed a repeat length-, PAM-, and strand-dependent reduction in the abundance of repeat-containing RNAs upon targeting dCas9 directly to repeat sequences. Aberrant splicing patterns were rescued in DM1 cells, and production of RAN peptides characteristic of DM1, DM2, andC9orf72-ALS/FTD cells was drastically decreased. Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in pathological RNA foci, rescue of chloride channel 1 protein expression, and decreased myotonia. These observations suggest that transcription of microsatellite repeat-containing RNAs is more sensitive to perturbation than transcription of other RNAs, indicating potentially viable strategies for therapeutic intervention.
BraCeR: Reconstruction of B-cell receptor sequences and clonality inference from single-cell RNA-sequencing
Authors: Lindeman Ida , Emerton Guy , Sollid Ludvig M. , Teichmann Sarah A. , Stubbington Michael J.T.
Published: September 2017

Reconstruction of antigen receptor sequences from single-cell RNA-sequencing (scRNA-seq) data allows the linking of antigen receptor usage to the full transcriptomic identity of individual B lymphocytes, without having to perform additional targeted repertoire sequencing (Rep-seq). Here we report BraCeR (freely available athttps://github.com/teichlab/bracer/), an extension of TraCeR [1], for reconstruction of paired full-length B-cell receptor sequences and inference of clonality from scRNA-seq data (Supplementary Note 1).
Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with signatures from post mortem adult brains
Authors: Hoffman Gabriel E. , Hartley Brigham J. , Flaherty Erin , Ladran Ian , Gochman Peter , Ruderfer Doug , Stahl Eli A. , Rapoport Judith , Sklar Pamela , Brennand Kristen J.
Published: September 2017

Whereas highly penetrant variants have proven well-suited to human induced pluripotent stem cell (hiPSC)-based models, the power of hiPSC-based studies to resolve the much smaller effects of common variants within the size of cohorts that can be realistically assembled remains uncertain. In developing a large case/control schizophrenia (SZ) hiPSC-derived cohort of neural progenitor cells and neurons, we identified and accounted for a variety of technical and biological sources of variation. Reducing the stochastic effects of the differentiation process by correcting for cell type composition boosted the SZ signal in hiPSC-based models and increased the concordance with post mortem datasets. Because this concordance was strongest in hiPSC-neurons, it suggests that this cell type may better model genetic risk for SZ. We predict a growing convergence between hiPSC and post mortem studies as both approaches expand to larger cohort sizes. For studies of complex genetic disorders, to maximize the power of hiPSC cohorts currently feasible, in most cases and whenever possible, we recommend expanding the number of individuals even at the expense of the number of replicate hiPSC clones.
Cued reactivation during slow-wave sleep induces connectivity changes related to memory stabilization
Authors: Berkers Ruud M.W.J. , Ekman Matthias , van Dongen Eelco V. , Takashima Atsuko , Barth Marcus , Paller Ken A. , Fernandez Guillen
Published: September 2017

Memory reprocessing following acquisition enhances memory consolidation. Specifically, neural activity during encoding is thought to be ‘replayed’ during subsequent slow-wave sleep (SWS). This natural tendency of memory replay can be induced by external cueing, known as “targeted memory reactivation”. Here, we analyzed data from a published study (van Dongen, Takashima, et al. 2012), where auditory cues reactivated learned visual object-location memories during SWS. Memory replay during sleep presumably involves a shift in connectivity across the brain. Therefore, we characterized the effects of memory reactivation on brain network connectivity using graph-theory. We found that cue presentation during SWS introduced increased network integration of the occipital cortex, a visual region that was also active during the object retrieval task. Importantly, enhanced network integration of the occipital cortex showed a behavioural benefit and predicted overnight memory stabilization. Furthermore, occipital cortex displayed enhanced connectivity with mnemonic regions, namely the hippocampus, parahippocampal gyrus, thalamus and medial prefrontal cortex during cue versus control sound presentation. Finally, network integration of early occipital cortex during cueing in SWS was related to increased activation of the bilateral parahippocampal gyrus, a region involved in coding for spatial associative information, at the post-sleep test. Together, these results support a neural mechanism where cue-induced replay during sleep promotes memory consolidation by increased integration of task-relevant perceptual regions with mnemonic regions.
An Algorithmic Information Calculus for Causal Discovery and Reprogramming Systems
Authors: Zenil Hector , Kiani Narsis A. , Marabita Francesco , Deng Yue , Elias Szabolcs , Schmidt Angelika , Ball Gordon , Tegnér Jesper
Published: September 2017

We introduce a new conceptual framework and a model-based interventional calculus to steer, manipulate, and reconstruct the dynamics and generating mechanisms of non-linear dynamical systems from partial and disordered observations based on the contributions of each of the systems, by exploiting first principles from the theory of computability and algorithmic information. This calculus entails finding and applying controlled interventions to an evolving object to estimate how its algorithmic information content is affected in terms ofpositiveornegativeshifts towards and away from randomness in connection to causation. The approach is an alternative to statistical approaches for inferring causal relationships and formulating theoretical expectations from perturbation analysis. We find that the algorithmic information landscape of a system runs parallel to its dynamic attractor landscape, affording an avenue for moving systems on one plane so they can be controlled on the other plane. Based on these methods, we advance tools for reprogramming a system that do not require full knowledge or access to the system’s actual kinetic equations or to probability distributions. This new approach yields a suite of universal parameter-free algorithms of wide applicability, ranging from the discovery of causality, dimension reduction, feature selection, model generation, a maximal algorithmic-randomness principle and a system’s (re)programmability index. We apply these methods to static (e.coli Transcription Factor network) and to evolving genetic regulatory networks (differentiating naïve from Th17 cells, and the CellNet database). We highlight their ability to pinpoint key elements (genes) related to cell function and cell development, conforming to biological knowledge from experimentally validated data and the literature, and demonstrate how the method can reshape a system’s dynamics in a controlled manner through algorithmic causal mechanisms.
Estimating the Mutational Fitness Effects Distribution during early HIV infection
Authors: Bons Eva , Bertels Frederic , Regoes Roland R
Published: September 2017

The evolution of HIV during acute infection is often considered a neutral process. Recent analysis of sequencing data from this stage of infection, however, showed high levels of shared mutations between independent viral populations. This suggests that selection might play a role in the early stages of HIV infection. We adapted an existing model for random evolution during acute HIV-infection to include selection. Simulations of this model were used to fit a global mutational fitness effects distribution (MFED) to sequencing data of theenvgene of individuals with acute HIV infection. Measures of sharing between viral populations were used as summary statistics to compare the data to the simulations. We confirm that evolution during acute infection is significantly different from neutral. The distribution of mutational fitness effects is best fit by distribution with a low, but significant fraction of beneficial mutations and a high fraction of deleterious mutations. While most mutations are neutral or deleterious in this model, about 5% of mutations is beneficial. These beneficial mutations will, on average, result in a small but significant increase in fitness. When assuming no epistasis, this indicates that at the moment of transmission HIV is near, but not on the fitness peak for early infection.
Genetic Analysis of Lodging in Diverse Maize Hybrids
Authors: Larsson Sara J. , Peiffer Jason A. , Edwards Jode W. , Ersoz Elhan S. , Flint-Garcia Sherry , Holland James B. , McMullen Michael D. , Tuinstra Mitchell R. , Romay M. Cinta , Buckler Edward S.
Published: September 2017

Damage caused by lodging is a significant problem in corn production that results in estimated annual yield losses of 5-20%. Over the past 100 years, substantial maize breeding efforts have increased lodging resistance by artificial selection. However, less research has focused on understanding the genetic architecture underlying lodging. Lodging is a problematic trait to evaluate since it is greatly influenced by environmental factors such as wind, rain, and insect infestation, which make replication difficult. In this study over 1,723 diverse inbred maize genotypes were crossed to a common tester and evaluated in five environments over multiple years. Natural lodging due to severe weather conditions occurred in all five environments. By testing a large population of genetically diverse maize lines in multiple field environments, we detected significant correlations for this highly environmentally influenced trait across environments and with important agronomic traits such as yield and plant height. This study also permitted the mapping of quantitative trait loci (QTL) for lodging. Several QTL identified in this study overlapped with loci previously mapped for stalk strength in related maize inbred lines. QTL intervals mapped in this study also overlapped candidate genes implicated in the regulation of lignin and cellulose synthesis.
Drosophila beta-Tubulin 97EF is upregulated at low temperature and stabilizes microtubules
Authors: Myachina Faina , Bosshardt Fritz , Bischof Johannes , Kirschmann Moritz , Lehner Christian F.
Published: September 2017

Summary statement

Ectotherms thrive within an often remarkable temperature range. At low temperature,betaTub97EF, a beta-tubulin paralog stabilizing microtubules, is upregulated in a tissue-specific manner in the flyDrosophila melanogaster.

Cells in ectotherms function normally within an often wide temperature range. As temperature dependence is not uniform across all the distinct biological processes, acclimation presumably requires complex regulation. The molecular mechanisms coping with the disruptive effects of temperature variation are still poorly understood. Interestingly, one of five different beta-tubulin paralogs,betaTub97EF, was among the genes up-regulated at low temperature in culturedDrosophilacells. As microtubules are known to be cold-sensitive, we analyzed whetherbetaTub97EFprotects microtubules at low temperatures. During development at the optimal temperature (25°C),betaTub97EFwas expressed in a tissue-specific pattern primarily in the gut. There, as well as in hemocytes, expression was increased at low temperature (14°C). WhilebetaTub97EFmutants were viable and fertile at 25°C, their sensitivity within the well-tolerated range was slightly enhanced during embryogenesis specifically at low temperatures. Changing beta-tubulin isoform ratios in hemocytes demonstrated that beta-Tubulin 97EF has a pronounced microtubule stabilizing effect. Moreover,betaTub97EFis required for normal microtubule stability in the gut. These results suggest thatbetaTub97EFup-regulation at low temperature contributes to acclimation by stabilizing microtubules.
ERAASR: An algorithm for removing electrical stimulation artifacts from multielectrode array recordings
Authors: O'Shea Daniel J. , Shenoy Krishna V.
Published: September 2017

Electrical stimulation is a widely used and effective tool in systems neuroscience, neural prosthetics, and clinical neurostimulation. However, electrical artifacts evoked by stimulation significantly complicate the detection of spiking activity on nearby recording electrodes. Here, we present ERAASR: an algorithm for Estimation and Removal of Artifacts on Arrays via Sequential principal components Regression. This approach leverages the similar structure of artifact transients, but not spiking activity, across simultaneously recorded channels on the array, across pulses within a train, and across trials. The effectiveness of the algorithm is demonstrated in macaque dorsal premotor cortex using acute linear multielectrode array recordings and single electrode stimulation. Large electrical artifacts appeared on all channels during stimulation. After application of ERAASR, the cleaned signals were quiescent on channels with no spontaneous spiking activity, whereas spontaneously active channels exhibited evoked spikes which closely resembled spontaneously occurring spiking waveforms. The ERAASR algorithm requires no special hardware and comprises sequential application of straightforward linear methods with intuitive parameters. Enabling simultaneous electrical stimulation and multielectrode array recording can help elucidate the causal links between neural activity and cognitive functions and enable the design and implementation of novel sensory protheses.
Highly expressed genes evolve under strong epistasis from a proteome-wide scan inE. coli
Authors: Girard Eric , Dasmeh Pouria , Serohijos Adrian W.R.
Published: September 2017

Epistasis or the non-additivity of mutational effects is a major force in protein evolution, but it has not been systematically quantified at the level of a proteome. Here, we estimated the extent of epistasis for 2,382 genes inE. coliusing several hundreds of orthologs for each gene within the classGammaproteobacteria. We found that the average epistasis is ~41% across genes in the proteome and that epistasis is stronger among highly expressed genes. This trend is quantitatively explained by the prevailing model of sequence evolution based on minimizing the fitness cost of protein unfolding and aggregation. Our results highlight the coupling between selection and epistasis in the long-term evolution of a proteome.
Functional characterization of theABFgene family in upland cotton (Gossypium hirsutumL.)
Authors: Kerr Tyson C. C. , Abdel-Mageed Haggag , Kang MiYoung , Cryer Dakota , Allen Randy D.
Published: September 2017

The AREB/ABF bZIP transcription factors play a pivotal role in abscisic acid-dependent abiotic stress-responsive gene expression. Despite the perennial damage and reduced productivity that result from water-deficit and unpredictable early season temperature fluctuations, these critical genes have not been previously examined in upland cotton (Gossypium hirsutum). Here, we report the isolation of theG. hirsutum ABFhomologs, characterization of their expression patterns in response to abiotic stress treatments, and examination of their functions through heterologous ectopic expression inArabidopsis. As expected for an allotetraploid,G. hirsutum ABFhomologs are present in the genome as homeologous pairs. These genes are differentially expressed, both among the homologs and within the homeologous pairs, in response to exogenous abscisic acid (ABA) application, dehydration, and chilling temperatures. Furthermore, heterologous ectopic expression of many of theG. hirsutum ABFgenes inArabidopsisconferred increased tolerance to water deficit and osmotic stress, as well as cold tolerance, in a gene specific manner. These results indicate theG. hirsutum ABFhomologs are functional inArabidopsisand, as in other species, are likely to play an essential role in the abiotic stress response.

Highlight

TheGossypium hirsutum ABFhomeologs are differentially expressed in response to abiotic stress, and their ectopic expression inArabidopsiscan confer increased water deficit tolerance.
The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells
Authors: Olney Kimberly C. , Nyer David B. , Vargas Daniel A. , Sayres Melissa A. Wilson , Haynes Karmella A.
Published: September 2017

Mounting evidence from genome-wide studies of cancer show that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-histone marks via its N-terminal H3K27me3-binding motif, and co-regulates sets of silenced genes. Here, we report transcriptome profiling analyses of PcTF-treated breast cancer model cell lines. We identified a set of 19 PcTF-upregulated genes, or PUGs, that were consistent across three distinct breast cancer cell lines. These genes are associated with the interferon response pathway. Our results demonstrate for the first time a chromatin-mediated interferon-related transcriptional response driven by an engineered fusion protein that physically links repressive histone marks with active transcription.
Origin of Slow Spontaneous Resting-State Neuronal Fluctuations in Brain Networks
Authors: Krishnan Giri P. , González Oscar C. , Bazhenov Maxim
Published: September 2017

Resting or baseline state low frequency (0.01-0.2 Hz) brain activity has been observed in fMRI, EEG and LFP recordings. These fluctuations were found to be correlated across brain regions, and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (< 0.05 Hz) fluctuations could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra and extracellular K+and Na+and intracellular Cl-ions, Na+/K+exchange pump, and KCC2 co-transporter. In the network model representing resting awake-like brain state, we observed slow fluctuations in the extracellular K+concentration, Na+/K+pump activation, firing rate of neurons and local field potentials. Holding K+concentration constant prevented generation of these fluctuations. The amplitude and peak frequency of this activity were modulated by Na+/K+pump, AMPA/GABA synaptic currents and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state networks observedin vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are observed as the resting-state fluctuations in fMRI and EEG recordings.
Mutation of Arabidopsis SMC4 identifies condensin as a corepressor of pericentromeric transposons and conditionally expressed genes
Authors: Wang Jing , Blevins Todd , Podicheti Ram , Haag Jeremy R. , Tan Ek Han , Wang Feng , Pikaard Craig S.
Published: September 2017

In eukaryotes, transcriptionally inactive loci are enriched within highly condensed heterochromatin. In plants, as in mammals, the DNA of heterochromatin is densely methylated and wrapped by histones displaying a characteristic subset of post-translational modifications. Growing evidence indicates that these chromatin modifications are not sufficient for silencing. Instead, they are prerequisites for further assembly of higher-order chromatin structures that are refractory to transcription but not fully understood. We show that silencing of transposons in the pericentromeric heterochromatin of Arabidopsis thaliana requires SMC4, a core subunit of condensins I and II, acting in conjunction with CG methylation by MET1 (DNA METHYLTRANSFERASE 1), CHG methylation by CMT3 (CHROMOMETHYLASE 3), the chromatin remodeler DDM1 (DECREASE IN DNA METHYLATION 1), and histone modifications, including histone H3 Lys 27 monomethylation (H3K27me1), imparted by ATXR5 and ATXR6. SMC4/condensin also acts within the mostly euchromatic chromosome arms to suppress conditionally expressed genes involved in flowering or DNA repair, including the DNA glycosylase ROS1, which facilitates DNA demethylation. Collectively, our genome-wide analyses implicate condensin in the suppression of hundreds of loci, acting in both DNA methylation-dependent and methylation-independent pathways.
Crystal structures of 2-(benzenecarbothioyloxy)ethyl benzenecarbothioate and 2-(benzenecarbothioyloxy)ethyl benzoate
Authors: Tanaka Syuto , Masu Hyuma , Sasanuma Yuji
Published: September 2017

The title compounds, C16H14O2S2and C16H14O3S, which are monomeric models (modelsDandE) for a polythionoester and a poly(ester-co-thionoester), respectively, crystallize in the space groupP21/cand are isostructural with each other. The molecule in each crystal is located on an inversion centre and has an all-transstructure. The asymmetric unit comprises one half-molecule. In the crystal, there are intermolecular C...S contacts [3.391 (3) and 3.308 (3) Å for modelsDandE, respectively] and C—H...π interactions, which form a layer structure parallel to thebcplane. The carbonyl and thiocarbonyl groups of the modelEcompound are each disordered over two equivalent sites about the inversion centre with equal occupancies.
N′-[(E)-4-Chlorobenzylidene]-2-(2,3-dimethylanilino)benzohydrazide
Authors: Jasinski Jerry P. , Akkurt Mehmet , Mohamed Shaaban K. , Dunkley Evan M. , Albayati Mustafa R.
Published: September 2017

In the title compound, C22H20ClN3O, the dihedral angle between the planes of the chlorophenyl and dimethylphenyl rings is 66.50 (9)°. These rings make dihedral angles 47.79 (8) and 69.24 (9)°, respectively, with the central benzene ring. In the crystal, molecules are linked into a three-dimensional supramolecular network by N—H...O, C—H...O hydrogen bonds and weak C—H...π interactions.
2-[((E)-{2-[(E)-(2-Hydroxybenzylidene)amino]benzyl}imino)methyl]phenol
Authors: Raghuvarman B. , Gayathri Jayagopi , Selvan Kumar Sangeetha , Aravindhan S. , Ponnuswamy M. N.
Published: September 2017

In the title hydroxyphenyl-substituted salophene compound, C21H18N2O2, there are two intramolecular O—H...N hydrogen bonds formingS(6) ring motifs. The phenol rings are inclined to one another by 65.9 (3)°, and by 0.0 (2) and 65.9 (2)°, respectively, to the central benzene ring. In the crystal, molecules are linked by a weak C—H...O contact forming chains along [010].
Living hours under pressure: flexibility loopholes in the Danish IR-model
Authors: Ilsøe Anna , Larsen Trine Pernille , Felbo-Kolding Jonas
Published: September 2017

Purpose

The purpose of this paper is to investigate the effect of part-time work on absolute wages. The empirical focus is wages and working hours in three selected sectors within private services in the Danish labour market – industrial cleaning, retail, hotels and restaurants – and their agreement-based regulation of working time and wages. Theoretically, this analysis is inspired by the concept of living hours, which addresses the interaction between working hours and living wages, but adds a new layer to the concept in that the authors also consider the importance of working time regulations for securing a living wage.

Design/methodology/approach

The paper builds on desk research of collective agreements and analysis of monthly administrative register data on wages and working hours of Danish employees from the period 2008-2014.

Findings

This analysis shows that the de facto hourly wages have increased since the global financial crisis in all three sectors. This is in accordance with increasing minimum wage levels in the sector-level agreements. The majority of workers in all three sectors work part-time. Marginal part-timers – 15 hours or less per week – make up the largest group of workers. The de facto hourly wage for part-timers, including marginal part-timers, is relatively close to the sector average. However, the yearly job-related income is much lower for part-time than for full-time workers and much lower than the poverty threshold. Whereas the collective agreement in industrial cleaning includes a minimum floor of 15 weekly working hours – this is not the case in retail, hotels and restaurants. This creates a loophole in the latter two sectors that can be exploited by employers to gain wage flexibility through part-time work.

Originality/value

The living wage literature usually focusses on hourly wages (including minimum wages via collective agreements or legislation). This analysis demonstrates that studies of low-wage work must include the number of working hours and working time regulations, as this aspect can have a dramatic influence on absolute wages – even in cases of hourly wages at relatively high levels. Part-time work and especially marginal part-time work can be associated with very low yearly income levels – even in cases like Denmark – if regulations do not include minimum working time floors. The authors suggest that future studies include the perspective of living hours to draw attention to the effect of low number of weekly hours on absolute income levels.
In defence of a university social work education
Authors: Thoburn June
Published: September 2017

Purpose

The purpose of this paper is to identify the particular characteristics and strengths of mainstream undergraduate and postgraduate university education for social workers.

Design/methodology/approach

A brief summary of the establishment of the honours degree or M-level qualification as the requirement for registration as a social worker in England is followed by a summary of the main aspects of “mainstream” social work courses. The values underpinning a “student” rather than a “trainee” route into social work are explored and some limited comparisons made with recently introduced fast-track specialist programmes. Where relevant, the student experience is contrasted with that of fast-track specialist trainees.

Findings

The paper concludes with a discussion of the potential impact on the social work profession and on agencies providing social work services of the cuts over the past few years in the numbers of students on “generalist” mainstream social work programmes.

Research limitations/implications

This is a conceptual paper. It recognises that more information is available on long-established university programmes than on the more recently available fast-track routes into social work and cites relevant research.

Practical implications

The paper points to the changing balance between numbers entering social work in England via mainstream and fast-track specialist programmes and argues for a fuller debate amongst all stakeholders as to whether this change is in the interest of the profession and those who need social work services.

Social implications

The author argues that the unequal level of funding between the different entry routes into social work is distorting choice (for students and future employers) between fast-track specialist and mainstream social work education. It is hypothesised that differences between the curricula and learning experiences of the two routes may have an impact on the social work service available to vulnerable people across age and needs groups. It also points to a potentially negative impact on social work education and the knowledge base of the reduction in numbers of academics with both social work practice experiences and research qualifications.

Originality/value

This is an original paper that draws on the author’s experience and the published research and grey literature cited.
Child protection in England: an emerging inequalities perspective
Authors: Bywaters Paul , Sparks Tim
Published: September 2017

Purpose

In the past 40 years, both health policy and educational policy in England have adopted commitments to reducing socially created inequalities. However, an inequalities perspective has only begun to emerge in relation to child protection, and child welfare services more widely. The purpose of this paper is to chart evidence of these green shoots of a new policy direction which focusses on two aspects: equalising service provision and outcomes for looked after children.

Design/methodology/approach

The paper provides an analysis of trends in policies as expressed in official documents, research studies and policy statements.

Findings

The paper outlines the argument for a more comprehensive approach to addressing inequalities in child protection and child welfare services, and concludes by suggesting some implications for policy and practice.

Originality/value

The paper develops the concept of an inequalities perspective in child protection and outlines key implications.