bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of heterogeneous tumour genomes with HeteroGenesis and in silico whole exome sequencing
Authors: Tanner Georgette , Westhead David R , Droop Alastair , Stead Lucy F
Published: January 2019

Tumour evolution results in progressive cancer phenotypes such as metastatic spread and treatment resistance. To better treat cancers, we must characterize tumour evolution and the genetic events that confer progressive phenotypes. This is facilitated by high coverage genome or exome sequencing. However, the best approach by which, or indeed whether, these data can be used to accurately model and interpret underlying evolutionary dynamics is yet to be confirmed. Establishing this requires sequencing data from appropriately heterogeneous tumours in which the exact trajectory and combination of events occurring throughout its evolution are known. We therefore developed HeteroGenesis: a tool to generate realistically evolved tumour genomes, which can be sequenced using weighted-Wessim (w-Wessim), an in silico exome sequencing tool that we have adapted from previous methods. HeteroGenesis simulates more complex and realistic heterogeneous tumour genomes than existing methods, can model different evolutionary dynamics, and enables the creation of multi-region and longitudinal data.

Availability and implementation

HeteroGenesis and w-Wessim are freely available under the GNU General Public Licence from https://github.com/GeorgetteTanner, implemented in Python and supported on linux and MS Windows.

Supplementary information

Supplementary data are available at Bioinformatics online.
Prevalence of Hepatitis B and Hepatitis D Virus Infections in the United States, 2011–2016
Authors: Patel Eshan U , Thio Chloe L , Boon Denali , Thomas David L , Tobian Aaron A R
Published: January 2019

Among adults in the 2011-2016 National Health and Nutrition Examination Survey (NHANES), the estimated prevalence of hepatitis B surface antigen (HBsAg) was 0.36% overall and 3.4% in non-Hispanic Asians. Among adult HBsAg carriers, 42% had antibodies to hepatitis delta virus (anti-HDV). Routine anti-HDV testing should be considered for HBsAg carriers.
The simplex geometry of graphs
Authors: Devriendt Karel , Van Mieghem Piet
Published: January 2019

Graphs are a central object of study in various scientific fields, such as discrete mathematics, theoretical computer science and network science. These graphs are typically studied using combinatorial, algebraic or probabilistic methods, each of which highlights the properties of graphs in a unique way. Here, we discuss a novel approach to study graphs: the simplex geometry (a simplex is a generalized triangle). This perspective, proposed by Miroslav Fiedler, introduces techniques from (simplex) geometry into the field of graph theory and conversely, via an exact correspondence. We introduce this graph-simplex correspondence, identify a number of basic connections between graph characteristics and simplex properties, and suggest some applications as example.
1. Family Law Practice and the First Interview
Authors: Sendall Jane
Published: January 2019

This chapter begins by identifying the skills that family lawyers must possess. These include technical skills such as advocacy, interviewing, negotiation, and writing; and ‘soft skills’, i.e. interpersonal and organizational skills, such as persuasiveness, tact, diplomacy, and time management. The discussion then turns to the professional conduct issues that are crucial to seeing a client for the first time, including confidentiality and money laundering. It also considers the importance of the first interview with the client and the client care letter.
4. The Single Family Court
Authors: Sendall Jane
Published: January 2019

This chapter provides an overview of the Single Family Court created in April 2014. It summarizes the effects of the Single Family Court and outlines who is involved in the judicial process within the new structure. It discusses how the allocation of cases within the Single Family Court are done by ‘gatekeepers’ and the new points of entry for cases.
8. Jurisdiction
Authors: Sendall Jane
Published: January 2019

This chapter deals with the European law governing jurisdiction in divorce and the international law concepts that are a feature of this area of law. It discusses the increasingly important question of jurisdiction in divorce proceedings, and explains the concepts of ‘domicile’ and ‘habitual residence’ as they apply to divorce proceedings.
11. Financial Orders Following Divorce or Dissolution
Authors: Sendall Jane
Published: January 2019

This chapter discusses the factors that a court will take into account when deciding on the division of money and property following a divorce or dissolution of a civil partnership. It introduces the main concepts in proceedings for financial orders under the Matrimonial Causes Act 1973; examines the factors considered by the court when deciding on financial orders; and discusses the principal case-law arising from proceedings for financial orders.
13. Pre-Marital Agreements
Authors: Sendall Jane
Published: January 2019

This chapter examines the nature of pre-marital agreements (PMAs), the enforceability of pre-marital agreements in proceedings for financial orders, and the potential developments in the enforceability of PMAs. Case-law dealing with the issue of PMAs is presented.
16. Protecting Assets and the Family Home in Financial Order Proceedings
Authors: Sendall Jane
Published: January 2019

This chapter discusses whether a client can protect assets in financial order proceedings, the provisions of s37 Matrimonial Causes Act 1973, and the availability of ‘home rights’ under the Family Law Act 1996. Section 37 MCA 1973 assists the parties and the courts in preventing the disposition of any assets by either party to the proceedings. An order can be made preventing a party from making a disposition with the intention of defeating the claim for financial relief or an order reviewing a disposition that has already been made.
22. Cohabitation
Authors: Sendall Jane
Published: January 2019

Cohabitating relationships are not covered by the same coherent body of law available to married couples or civil partners. Many cohabitants mistakenly believe that they acquire legal rights after a number of years of cohabiting, but this is incorrect. Many clients are shocked to find they have few legal remedies and those available are far from straightforward. This chapter begins with a comparison of marriage, civil partnership, and cohabitation. It then discusses the law on cohabitation contracts and future developments on cohabitation.
25. Parental Responsibility
Authors: Sendall Jane
Published: January 2019

Parental responsibility (PR) is one of the most important concepts in the Children Act 1989. This chapter discusses the nature and scope of PR, and how it is acquired. It covers the law on automatic parental responsibility; how unmarried fathers can acquire PR; and PR for non-natural parents.
27. Private Children Law Procedure
Authors: Sendall Jane
Published: January 2019

This chapter covers the basic procedure for a s8 Children Act 1989 (CA 1989) order. It discusses who is eligible to apply for an order under s8 CA 1989; public funding available for proceedings under the CA 1989; and the procedure for obtaining an order under the CA 1989 in private law proceedings.
28. Child Abduction
Authors: Sendall Jane
Published: January 2019

This chapter focuses on the issue of parental child abduction, i.e. the removal of children by a parent to another country without the permission of the other parent or the permission of the court. It examines the phenomenon of parental child abduction; the national and international law assisting parents seeking the return of a child; and the law and procedure relevant to preventing child abduction.
29. Children in Local Authority Care
Authors: Sendall Jane
Published: January 2019

This chapter examines the role of local authorities in protecting the child from harm and the orders available under the Children Act 1989, which are used in cases of alleged harm to children. It explains the ‘threshold criteria’—the standard that the court uses to decide whether an order should be made.
31. Public Children Procedure
Authors: Sendall Jane
Published: January 2019

This chapter examines the procedural issues involved in public children law proceedings. It discusses the representation of the child; steps to be taken before proceedings; the issue of proceedings; the first appointment; the case management hearing and advocates’ meeting; the issue resolution hearing; and the final hearing.
32. Child Protection Conferences
Authors: Sendall Jane
Published: January 2019

A local authority’s investigation into a child’s health and development includes a case conference so that information about the child can be shared by those involved with the child and family. This chapter discusses the function of a child protection conference in public children law and the role of a solicitor in the conference.
34. Protection under the Family Law Act 1996: Occupation Orders
Authors: Sendall Jane
Published: January 2019

The Family Law Act 1996 allows a court to make occupation orders to regulate the occupation of the family home. This chapter discusses the effect of occupation orders, the tests for each order, and which order to choose for the client.
35. Protection under the Family Law Act 1996: Emergency Protection and Enforcement
Authors: Sendall Jane
Published: January 2019

This chapter discusses the circumstances in which an order under the Family Law Act 1996 (FLA 1996) will be made without notice to the other party to proceedings; and the availability and methods of enforcement of orders made under the FLA 1996. A client who requires protection urgently is dealt with by applying for an order without notice. The court can only make an order without notice if there is risk of significant harm to the applicant, or the applicant will be deterred from pursuing the application, or the respondent is avoiding service.
37. Protection from Harassment
Authors: Sendall Jane
Published: January 2019

Family lawyers may be consulted by those who are being harassed or stalked by someone who is not an associated person. This chapter discusses the law on harassment and the remedies available to clients not protected by the Family Law Act 1996. It details the Protection from Harassment Act 1997, which was enacted to assist those suffering harassment through stalking, antisocial behaviour, or racial harassment.
Unpacking ‘the cloud’: a framework for implementing public health approaches to palliative care
Authors: Pfaff Kathryn A , Dolovich Lisa , Howard Michelle , Sattler Deborah , Zwarenstein Merrick , Marshall Denise
Published: January 2019

Designing and implementing population-based systems of care that address the social determinants of health, take action on multiple levels, and are guided by evidence-based principles is a pressing priority, and an international challenge. Aging persons are a priority demographic whose health needs span physical, psychosocial and existential care domains, increase in the last year of life, are often poorly coordinated and therefore remain unmet. Compassionate communities (CCs) are an example of a public health approach that fully addresses the holistic healthcare needs of those who are aging and nearing end of life. The sharing of resources, tools, and innovations among implementers of CCs is occurring globally. Although this can increase impact, it also generates complexity that can complicate robust evaluation. When initiating population health level projects, it is important to clearly define and organize concepts and processes that are proposed to influence the health outcomes. The Health Impact Change Model (HICM) was developed to unpack the complexities associated with the implementation and evaluation of a Canadian CC intervention. The HICM offers utility for citizens, leaders and decision-makers who are engaged in the implementation of population health level strategies or other social approaches to care, such as compassionate cities and age or dementia-friendly communities. The HICM’s concepts can be adapted to address a community’s healthcare context, needs, and goals for change. We share examples of how the model’s major concepts have been applied in the development, evaluation and spread of a complex CC approach.
EAP1 regulation of GnRH promoter activity is important for human pubertal timing
Authors: Mancini Alessandra , Howard Sasha R , Cabrera Claudia P , Barnes Michael R , David Alessia , Wehkalampi Karoliina , Heger Sabine , Lomniczi Alejandro , Guasti Leonardo , Ojeda Sergio R , Dunkel Leo
Published: January 2019

The initiation of puberty is orchestrated by an augmentation of gonadotropin-releasing hormone (GnRH) secretion from a few thousand hypothalamic neurons. Recent findings have indicated that the neuroendocrine control of puberty may be regulated by a hierarchically organized network of transcriptional factors acting upstream of GnRH. These include enhanced at puberty 1 (EAP1), which contributes to the initiation of female puberty through transactivation of the GnRH promoter. However, no EAP1 mutations have been found in humans with disorders of pubertal timing. We performed whole-exome sequencing in 67 probands and 93 relatives from a large cohort of familial self-limited delayed puberty (DP). Variants were analyzed for rare, potentially pathogenic variants enriched in case versus controls and relevant to the biological control of puberty. We identified one in-frame deletion (Ala221del) and one rare missense variant (Asn770His) in EAP1 in two unrelated families; these variants were highly conserved and potentially pathogenic. Expression studies revealed Eap1 mRNA abundance in peri-pubertal mouse hypothalamus. EAP1 binding to the GnRH1 promoter increased in monkey hypothalamus at the onset of puberty as determined by chromatin immunoprecipitation. Using a luciferase reporter assay, EAP1 mutants showed a reduced ability to trans-activate the GnRH promoter compared to wild-type EAP1, due to reduced protein levels caused by the Ala221del mutation and subcellular mislocation caused by the Asn770His mutation, as revealed by western blot and immunofluorescence, respectively. In conclusion, we have identified the first EAP1 mutations leading to reduced GnRH transcriptional activity resulting in a phenotype of self-limited DP.
Janzen’s Hypothesis Meets the Bogert Effect: Connecting Climate Variation, Thermoregulatory Behavior, and Rates of Physiological Evolution
Authors: Muñoz M M , Bodensteiner B L
Published: January 2019

Understanding the motors and brakes that guide physiological evolution is a topic of keen interest, and is of increasing importance in light of global climate change. For more than half a century, Janzen’s hypothesis has been used to understand how climatic variability influences physiological divergence across elevation and latitude. At the same time, there has been increasing recognition that behavior and physiological evolution are mechanistically linked, with regulatory behaviors often serving to dampen environmental selection and stymie evolution (a phenomenon termed the Bogert effect). Here, we illustrate how some aspects of Janzen’s hypothesis and the Bogert effect can be connected to conceptually link climate, behavior, and rates of physiological evolution in a common framework. First, we demonstrate how thermal heterogeneity varies between nighttime and daytime environments across elevation in a tropical mountain. Using data from Hispaniolan Anolis lizards, we show how clinal variation in cold tolerance is consistent with thermally homogenous nighttime environments. Elevational patterns of heat tolerance and the preferred temperature, in contrast, are best explained by incorporating the buffering effects of thermoregulatory behavior in thermally heterogeneous daytime environments. In turn, climatic variation and behavior interact to determine rates of physiological evolution, with heat tolerance and the preferred temperature evolving much more slowly than cold tolerance. Conceptually bridging some aspects of Janzen’s hypothesis and the Bogert effect provides an integrative, cohesive framework illustrating how environment and behavior interact to shape patterns of physiological evolution.
Rib Motions Don’t Completely Hinge on Joint Design: Costal Joint Anatomy and Ventilatory Kinematics in a Teiid Lizard, Salvator merianae
Authors: Capano J G , Moritz S , Cieri R L , Reveret L , Brainerd E L
Published: January 2019

Rib rotations contribute to lung ventilation in most extant amniotes. These rotations are typically described as bucket-handle rotation about a dorsoventral axis, caliper rotation about a craniocaudal axis, and pump-handle rotation about a mediolateral axis. A synapomorphy for Lepidosauria is single-headed costovertebral articulations derived from the ancestral double-headed articulations of most amniotes. With a single articular surface, the costovertebral joints of squamates have the potential to rotate with three degrees-of-freedom (DOFs), but considerable variation exists in joint shape. We compared the costovertebral morphology of the Argentine black and white tegu, Salvator merianae, with the green iguana, Iguana iguana, and found that the costovertebral articulations of I. iguana were hemispherical, while those of S. merianae were dorsoventrally elongated and hemiellipsoidal. We predicted that the elongate joints in S. merianae would permit bucket-handle rotations while restricting caliper and pump-handle rotations, relative to the rounded joints of I. iguana. We used X-ray reconstruction of moving morphology to quantify rib rotations during breathing in S. merianae for comparison with prior work in I. iguana. Consistent with our hypothesis, we found less caliper motion in S. merianae than in I. iguana, but unexpectedly found similar pump-handle magnitudes in each species. The dorsoventrally elongate costovertebral morphology of S. merianae may provide passive rib support to reduce the conflict between locomotion and ventilation. Moreover, the observation of multiple DOFs during rib rotations in both species suggests that permissive costovertebral morphology may be more related to the biological roles of ribs outside of ventilation and help explain the evolution of this trait.
Lithophagy Prolongs Voluntary Dives in American alligators (Alligator mississippiensis)
Authors: Uriona T J , Lyon M , Farmer C G
Published: January 2019

Many vertebrates ingest stones, but the function of this behavior is not fully understood. We tested the hypothesis that lithophagy increases the duration of voluntary dives in juvenile American alligators (Alligator mississippiensis). After ingestion of granite stones equivalent to 2.5% of body weight, the average duration of dives increased by 88% and the maximum duration increased by 117%. These data are consistent with the hypothesis that gastroliths serve to increase specific gravity, and that the animals compensate by increasing lung volume, thereby diving with larger stores of pulmonary oxygen.
Novel displays of patient information in critical care settings: a systematic review
Authors: Waller Rosalie G , Wright Melanie C , Segall Noa , Nesbitt Paige , Reese Thomas , Borbolla Damian , Del Fiol Guilherme
Published: January 2019

Objective

Clinician information overload is prevalent in critical care settings. Improved visualization of patient information may help clinicians cope with information overload, increase efficiency, and improve quality. We compared the effect of information display interventions with usual care on patient care outcomes.

Materials and Methods

We conducted a systematic review including experimental and quasi-experimental studies of information display interventions conducted in critical care and anesthesiology settings. Citations from January 1990 to June 2018 were searched in PubMed and IEEE Xplore. Reviewers worked independently to screen articles, evaluate quality, and abstract primary outcomes and display features.

Results

Of 6742 studies identified, 22 studies evaluating 17 information displays met the study inclusion criteria. Information display categories included comprehensive integrated displays (3 displays), multipatient dashboards (7 displays), physiologic and laboratory monitoring (5 displays), and expert systems (2 displays). Significant improvement on primary outcomes over usual care was reported in 12 studies for 9 unique displays. Improvement was found mostly with comprehensive integrated displays (4 of 6 studies) and multipatient dashboards (5 of 7 studies). Only 1 of 5 randomized controlled trials had a positive effect in the primary outcome.

Conclusion

We found weak evidence suggesting comprehensive integrated displays improve provider efficiency and process outcomes, and multipatient dashboards improve compliance with care protocols and patient outcomes. Randomized controlled trials of physiologic and laboratory monitoring displays did not show improvement in primary outcomes, despite positive results in simulated settings. Important research translation gaps from laboratory to actual critical care settings exist.
The Role of the Canadian Association of Chiefs of Police in Supporting the Professionalization of Police in Canada
Authors: Montgomery Ruth
Published: January 2019

The public deserves and expects professional and accountable policing. The need and desire to maintain and build public trust and respect in policing in dynamic, complex, and constantly evolving political, socio-economic, technological, and demographic contexts has driven increased discussion and examination of professionalization of policing. Effective and efficient policing today requires police leaders who are innovative, have political acumen and agile decision-making capacity, and can engage with a variety of actors at multiple levels to address public safety and security issues. Police leaders are also charged with ensuring that police officers at all levels have the education, knowledge, skills and competencies, and supports needed to solve crimes and problems, enforce laws, and prevent crime. The Commonwealth countries of England, Wales, Australia, and New Zealand have established professional bodies to regulate policing and address these requirements. This review uses identified characteristics of professions as a framework for comparing the work of these associations with contributions the Canadian Association of Chiefs has made in supporting, preparing, and professionalizing policing in Canada. It concludes by comparing the approaches to police professionalization in England, Wales, Australia, New Zealand, and Canada.
Sequencing of Chemotherapy and Radiotherapy for Newly Diagnosed Anaplastic Oligodendroglioma and Oligoastrocytoma
Authors: Ryckman Jeffrey M. , Surkar Swati M. , Haque Waqar , Butler E. Brian , Teh Bin S. , Verma Vivek
Published: January 2019

Introduction:

Adjuvant management of anaplastic oligodendrogliomas (AOs) and anaplastic oligoastrocytomas (AOAs) is guided by 2 seminal phase III trials, one of which utilized radiotherapy (RT) followed by chemotherapy (CT) (RT-CT), and the other in which CT was followed by RT (CT-RT). Both paradigms are endorsed by the National Comprehensive Cancer Network because no direct comparison in the first-line (nonprogressive) setting has been performed to date. This study of a contemporary national database sought to evaluate practice patterns and outcomes between both approaches.

Materials and Methods:

The National Cancer Database (NCDB) was queried for newly diagnosed AO/AOA treated with postoperative sequential CT-RT or RT-CT. Multivariable logistic regression ascertained factors independently associated with delivery of a particular paradigm. Overall survival (OS) between cohorts was compared using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling evaluated factors associated with OS.

Results:

Of 225 patients, 19 (8.4%) received CT-RT and 206 (91.6%) underwent RT-CT. Groups were well-balanced, although CT-RT was more often administered to men (P=0.009) and AOs (P=0.037). Median follow-up was 58 months. Median OS in the CT-RT cohort was 93 months (95% confidence interval, 37-150 mo), and 107 months (95% confidence interval, 72-142 mo) in the RT-CT group (P=0.709). Therapy sequence was not associated with OS on univariate (P=0.709) or multivariate (P=0.257) assessment.

Conclusions:

In the United States, most AO/AOA patients receiving sequential therapy undergo RT followed by CT. No differences in survival were observed with either approach; this addresses a knowledge gap and confirms that both paradigms are appropriate in the first-line setting.
Rational choice of social group size in mosquitofish
Authors: Reding Luke , Cummings Molly E.
Published: January 2019

Choice of social group can affect the likelihood of survivorship and reproduction for social species. By joining larger social groups—shoals—small freshwater fish like the mosquitofishGambusia affiniscan reduce predation risk and forage more efficiently. We tested shoal choice in mosquitofish to determine whether such choices are economically rational, i.e. consistent and optimal. Although many studies of decision-making assume rational choice, irrational decision-making is common and occurs across contexts. We tested rationality of shoaling decisions by testing the constant ratio rule, which states that the relative preference for two options should not change in the presence of a third option. Female mosquitofish upheld this rule when tested for shoal preference based on group size. Our results contrast with other studies showing violations of the constant ratio rule in foraging and mate choice decision-making contexts. These results suggest that decisions that immediately influence survivorship or decision-making along a single dimension may favour rational decision-making.
The social evolution of sleep: sex differences, intragenomic conflicts and clinical pathologies
Authors: Faria Gonçalo S. , Varela Susana A. M. , Gardner Andy
Published: January 2019

Sleep appears to be essential for most animals, including humans. Accordingly, individuals who sacrifice sleep are expected to incur costs and so should only be evolutionarily favoured to do this when these costs are offset by other benefits. For instance, a social group might benefit from having some level of wakefulness during the sleeping period if this guards against possible threats. Alternatively, individuals might sacrifice sleep in order to gain an advantage over mate competitors. Here, we perform a theoretical analysis of the social evolutionary pressures that drive investment into sleep versus wakefulness. Specifically, we: investigate how relatedness between social partners may modulate sleeping strategies, depending upon whether sleep sacrifice is selfish or altruistic; determine the conditions under which the sexes are favoured to adopt different sleeping strategies; identify the potential for intragenomic conflict between maternal-origin versus paternal-origin genes regarding an individual's sleeping behaviour; translate this conflict into novel and readily testable predictions concerning patterns of gene expression; and explore the concomitant effects of different kinds of mutations, epimutations, and uniparental disomies in relation to sleep disorders and other clinical pathologies. Our aim is to provide a theoretical framework for future empirical data and stimulate further research on this neglected topic.
Human children but not chimpanzees make irrational decisions driven by social comparison
Authors: Herrmann Esther , Haux Lou M. , Zeidler Henriette , Engelmann Jan M.
Published: January 2019

Human evolutionary success is often argued to be rooted in specialized social skills and motivations that result in more prosocial, rational and cooperative decisions. One manifestation of human ultra-sociality is the tendency to engage in social comparison. While social comparison studies typically focus on cooperative behaviour and emphasize concern for fairness and equality, here we investigate the competitive dimension of social comparison: a preference for getting more than others, expressed in a willingness to maximize relative payoff at the cost of absolute payoff. Chimpanzees and human children (5–6- and 9–10-year-olds) could decide between an option that maximized their absolute payoff (but put their partner at an advantage) and an option that maximized their relative payoff (but decreased their own and their partner's payoff). Results show that, in contrast to chimpanzees and young children, who consistently selected the rational and payoff-maximizing option, older children paid a cost to reduce their partner's payoff to a level below their own. This finding demonstrates that uniquely human social skills and motivations do not necessarily lead to more prosocial, rational and cooperative decision-making.
Leaf-cutter ants engineer large nitrous oxide hot spots in tropical forests
Authors: Soper Fiona M. , Sullivan Benjamin W. , Osborne Brooke B. , Shaw Alanna N. , Philippot Laurent , Cleveland Cory C.
Published: January 2019

Though tropical forest ecosystems are among the largest natural sources of the potent greenhouse gas nitrous oxide (N
2
O), the spatial distribution of emissions across landscapes is often poorly resolved. Leaf cutter ants (LCA;
Atta
and
Acromyrmex,
Myrmicinae) are dominant herbivores throughout Central and South America, and influence multiple aspects of forest structure and function. In particular, their foraging creates spatial heterogeneity by concentrating large quantities of organic matter (including nitrogen, N) from the surrounding canopy into their colonies, and ultimately into colony refuse dumps. Here, we demonstrate that refuse piles created by LCA species
Atta colombica
in tropical rainforests of Costa Rica provide ideal conditions for extremely high rates of N
2
O production (high microbial biomass, potential denitrification enzyme activity, N content and anoxia) and may represent an unappreciated source of heterogeneity in tropical forest N
2
O emissions. Average instantaneous refuse pile N
2
O fluxes surpassed background emissions by more than three orders of magnitude (in some cases exceeding 80 000 µg N
2
O-N m
−2
h
−1
) and generating fluxes comparable to or greater than those produced by engineered systems such as wastewater treatment tanks. Refuse-concentrating
Atta
species are ubiquitous in tropical forests, pastures and production ecosystems, and increase density strongly in response to disturbance. As such, LCA colonies may represent an unrecognized greenhouse gas point source throughout the Neotropics.
Increased signal diversity/complexity of spontaneous EEG, but not evoked EEG responses, in ketamine-induced psychedelic state in humans
Authors: Farnes Nadine , Juel Bjørn E. , Nilsen André S. , Romundstad Luis G. , Storm Johan F.
Published: January 2019

Objective

How and to what extent electrical brain activity is affected in pharmacologically altered states of consciousness, where it is mainly the phenomenological content rather than the level of consciousness that is altered, is not well understood. An example is the moderately psychedelic state caused by low doses of ketamine. Therefore, we investigated whether and how measures of evoked and spontaneous electroencephalographic (EEG) signal diversity are altered by sub-anaesthetic levels of ketamine compared to normal wakefulness, and how these measures relate to subjective assessments of consciousness.

Methods

High-density electroencephalography (EEG, 62 channels) was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and after administration of sub-anaesthetic doses of ketamine in an open-label within-subject design. Evoked signal diversity was assessed using the perturbational complexity index (PCI), calculated from the global EEG responses to local TMS perturbations. Signal diversity of spontaneous EEG, with eyes open and eyes closed, was assessed by Lempel Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE).

Results

Although no significant difference was found in the index of TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all the three measures of spontaneous EEG signal diversity showed significantly increased values in the sub-anaesthetic ketamine condition. This increase in signal diversity also correlated with subjective assessment of altered states of consciousness. Moreover, spontaneous signal diversity was significantly higher when participants had eyes open compared to eyes closed, both during normal wakefulness and during influence of sub-anaesthetic ketamine doses.

Conclusion

The results suggest that PCI and spontaneous signal diversity may be complementary and potentially measure different aspects of consciousness. Thus, our results seem compatible with PCI being indicative of the brain’s ability to sustain consciousness, as indicated by previous research, while it is possible that spontaneous EEG signal diversity may be indicative of the complexity of conscious content. The observed sensitivity of the latter measures to visual input seems to support such an interpretation. Thus, sub-anaesthetic ketamine may increase the complexity of both the conscious content (experience) and the brain activity underlying it, while the level, degree, or general capacity of consciousness remains largely unaffected.
Kinetic Analysis of Bacteriophage Sf6 Binding to Outer Membrane Protein A Using Whole Virions
Authors: Hubbs Natalia B. , Whisby-Pitts Mareena M. , McMurry Jonathan L.
Published: January 2019

For successful infection, viruses must recognize their respective host cells. A common mechanism of host recognition by viruses is to utilize a portion of the host cell as a receptor. Bacteriophage Sf6, which infects Shigella flexneri, uses lipopolysaccharide as a primary receptor and then requires interaction with a secondary receptor, a role that can be fulfilled by either outer membrane proteins (Omp) A or C. Our previous work showed that specific residues in the loops of OmpA mediate Sf6 infection. To better understand Sf6 interactions with OmpA loop variants, we determined the kinetics of these interactions through the use of biolayer interferometry, an optical biosensing technique that yields data similar to surface plasmon resonance. Here, we successfully tethered whole Sf6 virions, determined the binding constant of Sf6 to OmpA to be 36 nM. Additionally, we showed that Sf6 bound to five variant OmpAs and the resulting kinetic parameters varied only slightly. Based on these data, we propose a model in which Sf6: Omp receptor recognition is not solely based on kinetics, but likely also on the ability of an Omp to induce a conformational change that results in productive infection.
Intermittent hormonal therapy shows similar outcome than SOC in ER+ breast cancer preclinical model
Authors: Enriquez-Navas Pedro M. , Garcia Libia , Abdalah Mahmoud , Stringfield Olya , Luddy Kimberly , Hassan Sabrina , Gillies Robert J. , Gatenby. Robert A.
Published: January 2019

Clinical breast cancers in which at least 10% of cells express the estrogen receptor are labeled as “ER positive.” First line therapy for these patients is typically continuous administration of anti-estrogen drugs at maximum tolerated dose (MTD) until progression. In the vast majority of patients, resistance to hormone therapy evolves in the breast cancer cells within 2 years leading to treatment failure and tumor progression. In prior studies, we have demonstrated continuous application of MTD chemotherapy results in evolutionary dynamics (termed “competitive release”) that accelerates proliferation of treatment-resistance populations. In contrast, evolution-informed application of treatment reduces drug administration to maintain substantial populations of therapy-sensitive cells to reduce proliferation of resistant phenotypes. Prior pre-clinical and clinical studies have shown this strategy can delay or prevent proliferation of resistant cells and prolong time to progression (TTP). We hypothesize that similar dynamics may be observed in hormonal therapy of ER+ breast cancers. Here we address two important dynamics. First, we consider a clinical scenario in which symptoms are sufficiently severe or life-threatening to require rapid and substantial tumor reduction. Can this be achieved while retaining evolutionary dynamics to subsequently delay proliferation of resistance? A second, related question is defining the cost of resistance to anti-estrogen therapy. Here, we investigated the evolutionary dynamics of resistance to anti-estrogen therapy using ER+ MCF-7 orthotropic xenografts treated with both continuous Tamoxifen as well as cycles in which estrogen stimulation is combined with estrogen suppression. As expected, continuous administration of anti-estrogen drugs successfully suppressed tumor growth. However we found that brief interruptions in drug administration permitted equal tumor control while administering up to 50% less drug and maintaining cell phenotypes that retained high levels of ER expression and lower levels of MDR1 expression. In follow-on experiments combining hormonal and chemo-therapies; we obtained similar tumor control to hormonal therapy alone but with more necrosis and significantly lower ER expression in the surviving population.
Mechanical instabilities of aorta drive blood stem cell production: a live study
Authors: Poullet Nausicaa , Golushko Ivan , Lorman Vladimir , Travnickova Jana , Chalin Dmitryi , Rochal Sergei , Parmeggiani Andrea , Kissa Karima
Published: January 2019

During embryogenesis of all vertebrates, haematopoietic stem/progenitor cells (HSPCs) extrude from the aorta by a complex process named Endothelial-to-Haematopoietic Transition (EHT). HSPCs will then colonize haematopoietic organs allowing haematopoiesis throughout adult life. The mechanism underlying EHT including the role of each aortic endothelial cell within the global aorta dynamics remains unknown. In the present study, we show for the first time that EHT involves the remodelling of individual cells within a collective migration of endothelial cells which is tightly orchestrated, resulting in HSPCs extrusion in the sub-aortic space without compromising aorta integrity. By performing a cross-disciplinary study which combines high resolution 4D imaging and theoretical analysis based on the concepts of classical mechanics, we propose that this complex developmental process is dependent on mechanical instabilities of the aorta preparing and facilitating the extrusion of HSPCs.
Spatial organization of the transcriptional regulatory network of Saccharomyces cerevisiae
Authors: Sun Dong-Qing , Tian Liu , Ma Bin-Guang
Published: January 2019

Transcriptional regulatory network (TRN) is a directed complex network composed of all regulatory interactions between transcription factors and corresponding target genes. Recently, the three-dimensional (3D) genomics studies have shown that the 3D structure of the genome makes a difference to the regulation of gene transcription, which provides us with a novel perspective. In this study, we constructed the TRN of the budding yeast Saccharomyces cerevisiae and placed it in the context of 3D genome model. We analyzed the spatial organization of the yeast TRN on four levels: global feature, central nodes, hierarchical structure and network motifs. Our results suggested that the TRN of S. cerevisiae presents an optimized structure in space to adapt to functional requirement.
Knock-knock, who’s there: Sex-coding, competition and the energetics of tapping communication in the tok-tok beetle,Psammodes striatus(Coleoptera: Tenebrionidae)
Authors: Lighton John R.B.
Published: January 2019

I describe the abdomino-substratal tapping communication system of a Southern African tenebrionid beetle,Psammodes striatus(Fabricius, 1775) (Coleoptera: Tenebrionidae: Molurini), using computer simulation of tapping signals and computer-assisted acquisition of precise response timing data, augmented with data from natural beetle-beetle communication. Communication consists of trains of 5 - 7 Hz taps in groups or trains separated by 2-3 sec intervals. Male beetles spontaneously produce groups of tap-trains with 8 - 18 taps per train. If other beetles reply, an alternating duet commences. Solitary female beetles do not tap spontaneously but respond to male tapping with short, distinctive tap-trains containing 4 – 6 taps; they ignore female signals. In contrast, extensive communication occurs between male beetles, the nature of which changes significantly if the stimulus call is typical of male or of female beetles. Inter-male communication consists of long tap-trains, but males interacting with females produce shorter tap-trains and engage in phonotactic behavior that is absent in inter-male communication. Females respond highly preferentially to inter-male communication, rather than to the signals produced spontaneously by single males. Finally, I propose a simple model of the selective advantages of this unusual communication system, and calculate its approximate energetic leverage over random locomotion (∼13x).
Protein Fold Determination by Assembling Extended Super-Secondary Structure Motifs Using Limited NMR Data
Authors: Pilla Kala Bharath
Published: January 2019

The 3D fold determination of proteins by computational algorithms guided by experimental restraints is a reliable and efficient approach. However, the current algorithms struggle with sampling the conformational space and scaling in performance with the increase in the size of the proteins. This paper demonstrates a new data-driven, time-efficient, heuristics algorithm that assembles the 3D structure of a protein from its elemental super-secondary structure motifs (Smotifs) using a limited number of nuclear magnetic resonance (NMR) derived restraints. The DINGO-NOE-RDC algorithm (3D assembly of Individual smotifs to Near-native Geometry as Orchestrated by limited nuclear Overhauser effects (NOE) and residual dipolar couplings (RDC)) leverages on the distance restraints recorded on methyl-methyl (CH3-CH3), methyl-amide (CH3-HN), and amide-amide (HN–HN) NOE contacts, and orientation restraints recorded via RDC on the backbone amide protons, to assemble the target’s Smotifs. Two conceptual advancements were made to bootstrap the structure determination from limited NMR restraints; first, expand the basic definition of a ‘Smotif’ and, second, employ a data driven approach for selection, scoring, ranking and clustering of Smotif assemblies. In contrast to existing methods, the DINGO-NOE-RDC algorithm does not use any force-fields, physical/empirical scoring functions or the target’s amino-acid sequence makeup. Additionally, the algorithm employs a universal Smotif library that applies to any target protein and, can generate numerically reproducible results. For a benchmark set of ten different targets with different topologies, ranging from 100-200 residues, the algorithm identified near-native Smotifs in all of them.
Gain-of-function mutations in the UNC-2/CaV2α channel lead to hyperactivity and excitation-dominant synaptic transmission in Caenorhabditis elegans
Authors: Huang Yung-Chi , Pirri Jennifer K. , Rayes Diego , Gao Shangbang , Mulcahy Ben , Grant Jeff , Saheki Yasunori , Francis Michael M. , Zhen Mei , Alkema Mark J.
Published: January 2019

Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel α1 subunit, UNC-2, which leads to increased calcium currents. unc-2(gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(gf) mutants unc-2(gf) mutants display increased cholinergic- and decreased GABAergic-transmission. Moreover, we reveal that and increased cholinergic transmission in unc-2(gf) mutants leads to reduction of GABA synapses in a TAX-6/calcineurin dependent manner. Our studies provide mechanistic insight into how CaV2 gain-of-function mutations disrupt excitation-inhibition balance in the nervous system.
BioSAILs: versatile workflow management for high-throughput data analysis
Authors: Rowe Jillian , Drou Nizar , Youssef Ayman , Gunsalus Kristin C.
Published: January 2019

Motivation

High-throughput analysis in the current era of systems biology encompasses a range of analysis workflows for different applications, such as transcriptomics, epigenetics, variant discovery, de novo genome assembly, etc. Many research institutes house a genomics core facility that is responsible for generating high-throughput sequencing data and often includes a core bioinformatics team that carries out data analysis. Core teams must both keep track of data and maintain numerous software packages and databases – which must be scalable according to ever-changing research needs – and they must allocate computational resources to them. Typical data analysis pipelines involve multiple software packages and require the ability to install, execute, and maintain software stacks on a variety of hardware/operating system configurations, including high-performance computing (HPC) facilities, stand-alone servers, and Cloud services. At the same time, individual researchers need to analyze their data and share their analysis steps with collaborators. Having to rely on ad hoc scripts and rigid internally developed pipelines is inefficient, difficult to track and maintain, and ultimately, limits the ability to adapt and evolve as research methods progress.

Results

Here, we present BioSAILs (Bioinformatics Standardized Analysis Information Layers), a scientific workflow management system (WMS) developed by the Core Bioinformatics team at NYU Abu Dhabi. BioSAILs comprises two central components, BioX command and HPCRunner command, supported by BioStacks software stacks. BioX structures executable workflows that may be either run directly on a desktop or lab server, or submitted by HPCRunner to HPC infrastructure or the Cloud. BioSAILs is supported by a range of pre-configured, customizable BioStacks software stacks for various applications (e.g. RNA-seq, de novo genome/transcriptome assembly, variant discovery, etc.) Software stacks are built using Conda and BioConda (6), have been pre-packaged into modules using EasyBuild, and can be deployed with or without BioSAILs. Within the BioSAILs WMS, users can also invoke commands that take advantage of containerized software in Docker (10) and Singularity (8). Finally, the BioSAILs web resource provides documentation, blog posts related to various BioSAILs analysis tasks, forums, knowledge base & FAQs, as well as an interactive web-based workflow editor/creator. BioSAILs is production-level software that has been in use as the main WMS at NYU Abu Dhabi for the past 2 years and is continuously developed and maintained by the core bioinformatics team.

Availability

BioSAILs is open source software, available under the GNU license. Online documentation, support and guides can be found at biosails.abudhabi.nyu.edu. The public Github project is available at Github – BioSAILs. HPC-Runner and BioX-Workflow can be installed through Conda using the BioConda channel.