bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivering WPS Protection in All Female Peacekeeping Force
Authors: Karim Sabrina M.
Published: December 2018

The UN Mission in Liberia (UNMIL) has been touted as one of the most successful UN Missions when it comes to providing peace, but also when it comes to gender equality. The mission was home to the first all-female–formed police unit and was one of the first to incorporate gender in its peacekeeping mandates. As such, it stands out as an example for other missions. Upon closer inspection, however, UNMIL still suffers from many challenges associated with implementing gender balancing and gender mainstreaming. This chapter explores the mission’s successes in increasing participation among female peacekeepers, as well as the protection roles that female peacekeepers occupied. It also highlights some of the existing challenges that UNMIL and other peacekeeping missions more broadly must overcome to better achieve the goals of the women, peace, and security agenda. While, UNMIL’s mandate noted the importance of WPS, female peacekeepers experienced restrictions to their mobility and interactions with locals that may have prevented them from reaching their full potential in providing protection and preventing violence.
WPS and Protection of Civilians
Authors: Hultman Lisa , Muvumba Sellström Angela
Published: December 2018

Protection of civilians has become a core feature of UN peacekeeping. A normative shift in the 1990s led to new mandates and priorities in peacekeeping operations. This has occurred in parallel to the policy shift toward emphasizing the security of women. This chapter asks whether these two goals—protection of civilians and the security of women—go hand in hand or if there are tensions in the way they are pursued. Expectations formulated by the Security Council are examined as well as the operational activities and priorities on the ground. This chapter suggests that as UN actors move away from a singular focus on the weapon of war narrative, the protection of civilians discourse will evolve and thus create space for greater consideration of the WPS agenda. It also argues that peace support operations that tackle values and attitudes through training may address gender hierarchies and relations, while also securing the safety of women through patrols and escorts.
WPS and the Convention against Torture
Authors: Huber Andrea , Rytter Therese Maria
Published: December 2018

This chapter assesses the extent to which UN Security Council Resolutions 1325 on WPS takes into account the international human rights framework against torture and ill-treatment of women and girls, notably the obligations of prohibition, prosecution, punishment, and protection against different forms of torture, including sexual violence and rape. Moreover, it examines whether the obligations under the UN Convention against Torture vis-à-vis women and girls are reflected in post-conflict situations, especially peacekeeping operations. This chapter ultimately seeks to determine how UN human rights mechanisms with a specific mandate relating to torture have addressed situations specific to women and girls in conflict and post-conflict situations.
Global Study
Authors: Coomaraswamy Radhika , Kenney Emily
Published: December 2018

This chapter examines the core recommendations set out in the report of the 2015 Global Study on the Implementation of United Nations Security Council 1325. Commissioned by the Security Council, the study was mandated to highlight examples of good practice, implementation gaps and challenges, as well as emerging trends and priorities for action. Drawing on three focus areas that emerged from the global study, this chapter considers the recommendations in the broader political context, in particular the global shift toward inclusive and sustainable peace and security. This chapter argues that providing transformative justice for women, ensuring gender-sensitive and inclusive conflict prevention strategies, and creating counterterrorism approaches which respect women’s autonomy and human rights are central to the WPS agenda. Moreover, it concludes that addressing women’s experiences during conflict requires a deeper analysis of the impact of new technologies of war on women.
The Challenge of Foreign Policy in the WPS Agenda
Authors: Hudson Valerie M. , Eason Lauren
Published: December 2018

Drawing on the cases of the United States and Sweden, this chapter considers the conceptual and practical issues associated with the implementation of a feminist foreign policy (FFP). While Foreign Minister Margot Wallstrom of Sweden is perhaps the most vocal and overt advocate of the concept, the US State Department under Hillary Clinton also arguably promoted policies that were feminist in nature. This chapter examines the conceptualization of the term “feminist foreign policy,” probing dimensions, contestations, and inconsistencies. It explores the inherent pitfalls and misconceptions surrounding FFP, as well as the positive contributions of policies that promote gender equality. This chapter concludes that while FFP is not inherently pacifist, it does prioritize peace, and thus engaging in military interventions and alliances requires careful consideration under feminist just war principles. Moreover, this chapter argues that the dissemination of gender equality norms act as a mechanism that facilitates a more stable, secure, and peaceful nation.
WPS and Conflict Prevention
Authors: Kapur Bela , Rees Madeleine
Published: December 2018

This chapter assesses the scholarship and strategies associated with conflict prevention. It identifies four transformative shifts that have the potential to prevent conflict, namely the development of transformative gender relations; the elimination of militarized power relations; recognition of the importance of restorative agency and the reimagining of development strategies to ensure that they are equitable. Drawing on examples of international and local institutions and initiatives, this chapter suggests that conflict prevention requires a holistic social, cultural, and political response that engages with a broad cross section of the community. We argue that conflict prevention is not merely a fool’s errand. To that end, we provide a practical, integrated roadmap for academics, policymakers, and field-based practitioners alike to connect local, national, regional, and global efforts for peace and security, sustainable development, and human rights.
WPS and Women’s Roles in Conflict-Prevention
Authors: George Nicole
Published: December 2018

This chapter examines the history of women’s conflict in Bougainville, an island territory that was plunged into conflict for a ten-year period in the late 1980s. Women’s conflict-prevention activities were influential at a range of levels and generated a broader momentum for peace in the territory, which has been widely recognized and celebrated. But the gendered continuities and ruptures that have become evident as Bougainville has transitioned from conflict to peace indicate the difficulties women have had in the longer-term in challenging the broader architecture of entitlement that shapes and restricts debate on post-conflict governance in Bougainville. The experiences of women in this conflict context are instructive, showing how a focus on women’s agency in peace-building can create opportunities for women in some areas of public and political life, but constrain their capacity to challenge restrictive or discriminatory gendered practices in others.
Women’s Roles in CVE
Authors: Eddyono Sri Wiyanti , Davies Sara E.
Published: December 2018

This chapter examines recent attempts to apply evolving ideas regarding women’s empowerment, leadership, and participation to the issue of preventing and countering violence extremism (P/CVE). Incorporation of the central tenants of the women, peace, and security agenda in the UN Security Council Resolution on P/CVE and the 2016 Global Strategy for Countering and Preventing Terrorism and Violent Extremism has been a crucial and welcome development. The Global Strategy promotes the integration of a gender perspective across the framework and a more targeted, specific focus on gender equality and women’s empowerment within high-risk situations. Moreover, as this chapter demonstrates, the Global Strategy acknowledges the diversity of women’s roles and their agency in different areas, particularly in the more private and less public spaces. This chapter argues that private spaces and relationships can be sources of power to secure peace and security. It suggests that more effort is needed to enhance, support, and upscale women’s human rights activities and organizations that seek to address the issues of P/CVE. Finally, this chapter concludes that the international community needs to recognize, respect, and support women’s roles in interfaith communities.
Dorsal Root Ganglion Neuron Types and Their Functional Specialization
Authors: Emery Edward C. , Ernfors Patrik
Published: December 2018

Primary sensory neurons of the dorsal root ganglion (DRG) respond and relay sensations that are felt, such as those for touch, pain, temperature, itch, and more. The ability to discriminate between the various types of stimuli is reflected by the existence of specialized DRG neurons tuned to respond to specific stimuli. Because of this, a comprehensive classification of DRG neurons is critical for determining exactly how somatosensation works and for providing insights into cell types involved during chronic pain. This article reviews the recent advances in unbiased classification of molecular types of DRG neurons in the perspective of known functions as well as predicted functions based on gene expression profiles. The data show that sensory neurons are organized in a basal structure of three cold-sensitive neuron types, five mechano-heat sensitive nociceptor types, four A-Low threshold mechanoreceptor types, five itch-mechano-heat–sensitive nociceptor types and a single C–low-threshold mechanoreceptor type with a strong relation between molecular neuron types and functional types. As a general feature, each neuron type displays a unique and predicable response profile; at the same time, most neuron types convey multiple modalities and intensities. Therefore, sensation is likely determined by the summation of ensembles of active primary afferent types. The new classification scheme will be instructive in determining the exact cellular and molecular mechanisms underlying somatosensation, facilitating the development of rational strategies to identify causes for chronic pain.
US Fertility Rates and Childbearing in American Economic History, 1800–2010
Authors: Bailey Martha J. , Hershbein Brad J.
Published: December 2018

Over the past two centuries, the United States has witnessed dramatic changes in fertility rates and childbearing. This chapter describes shifts in childbearing and family size from 1800 to 2010 and describes the role of different factors in this evolution. Demand factors such as industrialization, urbanization, rising family incomes, public health improvements, and the growth in women’s wages generally reduced the benefits and raised the costs of having many children. Supply factors such as increases in infant and child survival and improvements in the technology of contraception and abortion have also altered parents’ decisions about their childbearing. This chapter summarizes the long-run trends in US fertility rates and completed childbearing, both overall and by mothers’ race/ethnicity and geography. Next, it evaluates evidence on the determinants of childbearing, including both economic and demographic explanations for these patterns. A final section weighs the evidence supporting the existence of two fertility transitions.
Natural Resources in American Economic History
Authors: Wright Gavin
Published: December 2018

This chapter surveys the role of natural resources in American economic history, from colonial times to the present. The central theme is that natural resources do indeed have a history: to a very considerable degree, American resource abundance has been “socially constructed” through responses to economic incentives, investments in transportation, and development of technologies of exploration and extraction using advanced forms of knowledge. During the nineteenth century, Americans adapted their technologies and consumption patterns toward wood to an extent unmatched in the world at that time. The country’s rise to world leadership in minerals was not based primarily on geological endowment, but on an accommodating legal environment, expansion of the infrastructure of public knowledge, and investment in higher mining education. Recent American developments in shale oil and shale gas confirm the historical generalization that natural resources are not given by nature but by policy choices and human behavior.
Housing in American Economic History
Authors: Snowden Kenneth , Fetter Daniel , Rose Jonathan
Published: December 2018

Housing finance in the United States has changed considerably since the late nineteenth century. Institutional lenders gradually displaced individual investors, experiments with securitization flourished and then receded, mortgage contracts evolved, and the Great Depression of the 1930s led to nationwide declines in real estate prices, a major housing finance crisis, and the advent of federal government involvement in the residential mortgage market with a slate of new programs. Over the same long period, home ownership has risen, though most of the increase was concentrated in the period from 1940 to 1960, and the quality of the housing stock has improved.
Welfare Policy
Authors: Fishback Price V.
Published: December 2018

The expansion of the safety net in the United States was one of the major changes in the economy in the twentieth century. The public safety net evolved from poverty relief programs run by local governments and private charities to a much larger system dominated by social insurance programs run by different mixtures of the federal and state governments. These included such social insurance programs as Social Security, workers’ compensation, unemployment insurance, and disability insurance, as well as the public assistance programs that are commonly described as welfare programs. This chapter surveys the work done by economic historians on how and why the US safety net expanded during the formative years of the early twentieth century and the impact of those changes.
Classic Philosophical Approaches to Lying and Deception
Authors: Mahon James Edwin
Published: December 2018

This chapter focuses on the classic philosophical approaches to lying and deception by Aristotle, Plato, and Socrates. It deals with the morality of lying. Two important traditions are traced back to Plato, who sought to justify lying under certain circumstances, and Aristotle, who condemned all lies. The views of the moral absolutists Augustine, Aquinas, and Kant are clearly influenced by Aristotle. Yet even Aristotle permitted certain types of lies, for instance, self-deprecating lies told by the magnanimous person. Therefore, Socrates, the teacher of Plato, can be seen as a better prospect for holding a moral absolutist view among the ancient Greeks. While being part of the moral absolutist tradition, the moral absolutists Augustine, Aquinas, and Kant sought to develop positions different from those founded on Plato and Aristotle.
Provincial Art
Authors: Busch Alexandra W. , von Hesberg Henner
Published: December 2018

In this chapter we give an idea of the characteristics and peculiarities of so-called ‘provincial art’ in Roman Germany. We shall focus in particular on images, but also occasionally on objects, recovered in the provinces of Germania Inferior, Germania Superior, Gallia Belgica, and Raetia. The emphasis will be less on the artistic value of the images and objects and much more on their capacity to convey information. Communication by means of images created a wide-ranging and diverse theatre of exchange; these images were often rigidly codified, or—for example when images were reproduced in series—mass-produced and hence standardized to project and propagate a specific vision. The use and attributes of the images are at the core of our considerations; we aim to provide an understanding of the language employed, of the images’ function as a medium of communication, and of the processes that underlay their production.
Prevalence of Viruses in Commercial Wine Grape Vineyards in Georgia
Authors: Brannen Phillip M. , Deom C. Michael , Alabi O. J. , Naidu Rayapati A.
Published: December 2018

Virus diseases are major constraints to Vitis vinifera wine grape production worldwide. Grapevine leafroll-associated virus 3 (GLRaV-3) was first confirmed in Georgia in 2008. The negative impacts of GLRaV-3, such as decreased fruit yield and quality, were confirmed from samples taken in 2009 and 2010. In light of these findings, studies were initiated to determine the prevalence and types of grapevine viruses present in vineyards in Georgia. Five vineyard blocks were visited during August and September of 2011 and 2012. Leaf samples were collected from a total of 50 grapevines showing symptoms of and suspected as being infected by grapevine leafroll disease (GLD). Samples from individual grapevines were extracted and tested separately for 20 grapevine viruses listed in standard virus indexing programs. Reverse transcription polymerase chain reaction (RT-PCR) or PCR, depending on the nature of the virus genome, was used to detect these viruses with species-specific primers. The results showed the presence of GLRaV-1, -2, -3, and -4 (strains 4, 5, and 6), grapevine virus B, grapevine rupestris stem pitting-associated virus, and grapevine red blotch virus. Many vineyards had multiple viruses detected from individual grapevines showing typical GLD or GLD-like symptoms.
Individual and Sexual Network Predictors of HIV Incidence Among Men Who Have Sex With Men in Nigeria
Authors: Nowak Rebecca G. , Mitchell Andrew , Crowell Trevor A. , Liu Hongjie , Ketende Sosthenes , Ramadhani Habib O. , Ndembi Nicaise , Adebajo Sylvia , Ake Julie , Michael Nelson L. , Blattner William A. , Baral Stefan D. , Charurat Manhattan E. ,   on behalf of the TRUST/RV368 Study Group
Published: December 2018

Background:

To date, HIV incidence studies among men who have sex with men (MSM) across sub-Saharan Africa have focused on studying sexual risk practices with less focus on sexual networks.

Setting:

TRUST/RV368 conducted in Abuja and Lagos, Nigeria, recruited MSM using respondent-driven sampling and followed HIV-negative men for incident infection over 4 years.

Methods:

Four-hundred forty-one HIV-uninfected MSM underwent a parallel rapid HIV testing algorithm every 3 months for up to 18 months. HIV incidence per 100 person-years (PY) and 95% confidence intervals (CIs) were estimated using Poisson regression. Individual and network characteristics were examined using multivariable Cox-proportional hazards regression adjusted and unadjusted for respondent-driven sampling weights.

Results:

Among cohort members with a median age of 23 years [interquartile range (IQR): 20–27], 81 HIV infections occurred over 527 PY (incidence 15.4/100 PY; 95% CI: 12.3 to 19.0). The incidence rate was highest among 16–19 year olds as compared to those 25 years or older (30.9/100 PY; 95% CI: 22.1 to 45.3 vs. 6.9/100 PY; 95% CI: 4.2 to 10.9, respectively). Individual determinants included receptive partnerships, condomless sex, no history of testing for HIV, and rectal gonorrhea. Sexual networks were larger and consisted of an older sexual partner, although there was no clustering by recruitment networks.

Conclusions:

These HIV incidence data reinforce the unmet HIV prevention needs among young MSM in Nigeria. Even in the context of emerging HIV diagnostic and prevention strategies, structural challenges including stigma and criminalization of same-sex practices highlight the need for novel implementation approaches in the context of MSM-friendly services.
A Rare Cause for Recurrent Implant-Related Inflammation of Orbit: Dacryocystitis
Authors: Gümüş Zehra Betül , Gümüş Nazim
Published: December 2018

Ultra-thin porous polyethylene has been widely preferred in orbital blow out fracture repair for many years as a safe and stable material. Delayed complications related to the implant in orbital blow out fracture repair are very rare and usually begin as a periorbital inflammation. Infections and tissue reaction to the foreign body are regarded as main causes for implant-related inflammation of which symptoms may vary among the patients and may involve subacute and chronic eyelid swelling, skin redness, pain, conjunctival injection, proptosis, and acute orbital inflammation.

Presented here is a patient of recurrent periorbital inflammation who underwent orbital floor repair with ultra-thin porous polyethylene sheet which was complicated by dacryocystitis in the late follow-up period.
Optogenetic stimulation of long-range inputs and functional characterization of connectivity in patch-clamp recordings in mouse brain slices
Authors: Richevaux Louis , Schenberg Louise , Beraneck Mathieu , Fricker Desdemona
Published: December 2018

Knowledge of cell type specific synaptic connectivity is a crucial prerequisite for understanding brain wide neuronal circuits. The functional investigation of long-range connections requires targeted recordings of single neurons combined with the specific stimulation of identified distant inputs. This is often difficult to achieve with conventional, electrical stimulation techniques, because axons from converging upstream brain areas may intermingle in the target region. The stereotaxic targeting of a specific brain region for virus-mediated expression of light sensitive ion channels allows to selectively stimulate axons coming from that region with light. Intracerebral stereotaxic injections can be used in well-delimited structures, such as the anterodorsal thalamic nuclei, and also in other subcortical or cortical areas throughout the brain. Here we describe a set of techniques for precise stereotaxic injection of viral vectors expressing channelrhodopsin in the anterodorsal thalamus, followed by photostimulation of their axon terminals in hippocampal slices. In combination with whole-cell patch clamp recording from a postsynaptically connected presubicular neuron, photostimulation of thalamic axons allows the detection of functional synaptic connections, their pharmacological characterization, and the evaluation of their strength in the brain slice preparation. We demonstrate that axons originating in the anterodorsal thalamus ramify densely in presubicular layers 1 and 3. The photostimulation of Chronos expressing thalamic axon terminals in presubiculum initiates short latency postsynaptic responses in a presubicular layer3 neuron, indicating a monosynaptic connection. In addition, biocytin filling of the recorded neuron and posthoc revelation confirms the layer localization and pyramidal morphology of the postsynaptic neuron. Taken together, the optogenetic stimulation of long-range inputs in ex vivo brain slices is a useful method to determine the cell-type specific functional connectivity from distant brain regions.
Can cancer GWAS variants modulate immune cells in the tumor microenvironment?
Authors: Zhang Yi , Manjunath Mohith , Yan Jialu , Baur Brittany A. , Zhang Shilu , Roy Sushmita , Song Jun S.
Published: December 2018

Genome-wide association studies (GWAS) have hitherto identified several genetic variants associated with cancer susceptibility, but the molecular functions of these risk modulators remain largely uncharacterized. Recent studies have begun to uncover the regulatory potential of non-coding GWAS SNPs by using epigenetic information in corresponding cancer cell types and matched normal tissues. However, this approach does not explore the potential effect of risk germline variants on other important cell types that constitute the microenvironment of tumor or its precursor. This paper presents evidence that the breast cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor infiltrating lymphocytes. CTSW is a candidate tumor-suppressor gene, with expression highly specific to immune cells and also positively correlated with breast cancer patient survival. Integrative analyses suggest a putative causative variant in a GWAS-linked enhancer in lymphocytes that loops to the 3’ end of CTSW through three-dimensional chromatin interaction. Our work thus poses the possibility that a cancer-associated genetic variant might regulate a gene not only in the cell of cancer origin, but also in immune cells in the microenvironment, thereby modulating the immune surveillance by T lymphocytes and natural killer cells and affecting the clearing of early cancer initiating cells.
Maladaptive coping strategies and neuroticism mediate the relationship between 5HTT-LPR polymorphisms and symptoms of anxiety in elite athletes.
Authors: Altamura Mario , Iuso Salvatore , D'Andrea Giovanna , D'Urso Francesca , Piccininni Carla , Angelini Eleonora , Francesco Sessa , Margaglione Maurizio , Padulo Caterina , Fairfield Beth , Petito Annamaria , Bellomo Antonello
Published: December 2018

Previous studies have suggested that genetic factors, personality traits and coping strategies might play independent and interacting roles in influencing stress-related anxiety symptoms. The aim of this study was to examine whether Neuroticism and maladaptive coping strategies mediate the association between the serotonin transporter gene-linked polymorphic region (5HTT-LPR) and symptoms of anxiety and depression in elite athletes who experience high levels of competitive stress. One hundred and thirty-three participants were genotyped for the 5-HTTLPR polymorphism and then asked to complete the Cope Orientation to Problems Experienced Inventory and the NEO Five-Factor Inventory. A path analysis was used to test the aforementioned hypothesis. The 5HTT-LPR was significantly associated with Neuroticism, the coping strategy of Focus on and Venting of Emotions (FVE) and symptoms of anxiety. FVE and Neuroticism mediated the association between the 5HTT-LPR and symptoms of anxiety (i.e., Cognitive Anxiety and Emotional Arousal Control). Also, Neuroticism was a mediator of the association between the 5HTT-LPR and FVE. Finally, FVE also mediated effects on the relationship between Neuroticism and symptoms of anxiety. Results suggest that the 5HTT-LPR may affect the susceptibility to develop symptoms of anxiety in elite athletes indirectly through mediation by FVE and Neuroticism.
Evolution of connections and cell types: integrating diffusion MR tractography with gene expression data highlights increased cortico-cortical projections in primates
Authors: Charvet Christine , Palani Arthi , Priya Kabaria Priya , Takahashi Emi
Published: December 2018

Diffusion MR tractography permits investigating the three-dimensional structure of cortical pathways as interwoven paths across the entire brain. We use high-resolution scans from diffusion spectrum imaging and high angular resolution diffusion imaging to investigate the evolution of cortical pathways within the euarchontoglire (i.e., primates, rodents) lineage. More specifically, we compare cortical fiber pathways between macaques (Macaca mulatta), marmosets (Callithrix jachus), and rodents (mice, Mus musculus). We integrate these observations with comparative analyses of Neurofilament heavy polypeptide (NEFH) expression across the cortex of mice and primates. We chose these species because their phylogenetic position serves to trace the early evolutionary history of the human brain. Our comparative analysis from diffusion MR tractography and NEFH expression demonstrates that the examined primates deviate from mice in possessing increased long-range cross-cortical projections, many of which course across the anterior to posterior axis of the cortex. Our study shows that integrating gene expression data with diffusion MR data is an effective approach in identifying variation in connectivity patterns between species. The expansion of cortico-cortical pathways and increased anterior to posterior cortical integration can be traced back to an extension of neurogenetic schedules during development in primates.
Dynamic 11C-PiB PET shows cerebrospinal fluid flow alterations in Alzheimer’s disease and multiple sclerosis
Authors: Schubert Julia J. , Veronese Mattia , Marchitelli Livia , Bodini Benedetta , Tonietto Matteo , Stankoff Bruno , Brooks David J. , Bertoldo Alessandra , Edison Paul , Turkheimer Federico E.
Published: December 2018

Cerebrospinal fluid (CSF) plays an important role in the clearance of solutes and maintenance of brain homeostasis. 11C-PiB PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer’s disease. The current study seeks to investigate the magnitude of 11C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer’s and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-beta tissue accumulation.

Methods

A set of Alzheimer’s and mild cognitive impairment subjects and a set of multiple sclerosis subjects with matched healthy controls underwent MRI and dynamic 11C-PiB PET. Manual lateral ventricle regions of interest were generated from MRI data. PET data was analysed using a simplified reference tissue model with cerebellum or a supervised reference region, for the Alzheimer’s and multiple sclerosis datasets, respectively. Magnitude of 11C-PiB signal in the lateral ventricles was calculated as area under curve from 35 to 80 minutes and standard uptake value ratio (SUVR) from 50 to 70 minutes. Compartmental modelling analysis was performed on a separate dataset containing Alzheimer’s and matched healthy control data with an arterial input function to further understand the kinetics of the lateral ventricular 11C-PiB signal.

Results

Analysis of variance revealed significant group differences in lateral ventricular SUVR across the Alzheimer’s, mild cognitive impairment, and healthy control groups (p=0.004). Additional pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer’s compared to healthy controls (p<0.001) and mild cognitive impairment (p=0.029). Lateral ventricular SUVR was also significantly lower in multiple sclerosis compared to healthy controls (p=0.008). Compartmental modelling analysis revealed significantly lower uptake rates of 11C-PiB signal from blood (p=0.005) and brain tissue (p=0.004) to the lateral ventricles in Alzheimer’s compared to healthy controls. This analysis also revealed significantly lower clearance of 11C-PiB signal out of the lateral ventricles in Alzheimer’s compared to healthy controls (p=0.002).

Conclusion

Overall, these results indicate that dynamic 11C-PiB PET can be used to observe pathological changes in cerebrospinal fluid dynamics and that cerebrospinal fluid-mediated clearance is reduced in Alzheimer’s disease and multiple sclerosis compared to healthy controls.
Forecasting when cells die during antibiotic exposure using stochastic gene expression
Authors: Rossi Nicholas A. , Meouche Imane El , Dunlop Mary J.
Published: December 2018

Antibiotic killing does not occur at a single, precise time for all cells within a population. Variability in time to death can be caused by stochastic expression of genes, resulting in differences in endogenous stress-resistance levels between individual cells in a population. This variability can be part of a bet-hedging strategy where cells leverage noise to ensure a subset of the population can tolerate the drug, while decreasing the overall cost of expressing resistance genes. We asked whether single-cell differences in gene expression prior to antibiotic addition were related to cell survival times after antibiotic exposure for a range of genes of diverse function. We quantified the time to death of single cells under antibiotic exposure in combination with expression of reporters. For some reporters, the time to cell death had a strong relationship with the initial expression level of the genes. Reporters that could forecast cell fate included stress response genes, but also genes involved in a variety of other cellular processes like metabolism. Our results highlight the single-cell level non-uniformity of antibiotic killing and also provide examples of key genes where cell-to-cell variation in expression prior to antibiotic exposure is strongly linked to extended durations of antibiotic survival.
svtools: population-scale analysis of structural variation
Authors: Larson David E. , Abel Haley J. , Chiang Colby , Badve Abhijit , Das Indraniel , Eldred James M. , Layer Ryan M. , Hall Ira M.
Published: December 2018

Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps – including deletions, duplications, mobile element insertions, inversions, and other rearrangements – in many thousands of human genomes. We show that this pipeline achieves similar variant detection performance to established per-sample methods (e.g., via LUMPY), while providing fast and affordable joint analysis at the scale of ≥100,000 genomes. These tools will help enable the next generation of human genetics studies.

Availability and Implementation

svtools is implemented in Python and freely available (MIT) fromhttps://github.com/hall-lab/svtools.

Contact

ihall@wustl.edu
Development of oocytes in a post-spawning Japanese eel Anguilla japonica Temminck & Schlegel in captivity
Authors: Tanaka Satoru , Okamura Akihiro , Mikawa Naomi , Yamada Yoshiaki , Horie Noriyuki , Utoh Tomoko , Zhang Huan , Oka Hideo P. , Tsukamoto Katsumi
Published: December 2018

It is generally believed that parent freshwater eels (Anguilla sp.) die soon after spawning on the assumption that eels are a semelparous (or monocyclic) fish (spawn once at the last stage of life) like Pacific salmonids. However, we observed for the first time a post-spawning female Anguilla japonica again possessed developing oocytes reaching the final maturation stage in captivity five months after the last spawning even without hormonal treatment. Here we describe information on this female about its biological characteristics including gonadal histology and endocrine profiles. The data suggest that lowering water temperature for a period of time is one of the important factors influencing spontaneous gonadal development in this specimen. We also discuss the possibility of induced multiple spawning of this species in captivity.
Swapping Birth and Death: Symmetries and Transformations in Phylodynamic Models
Authors: Stadler Tanja , Steel Mike
Published: December 2018

Stochastic birth–death models provide the foundation for studying and simulating evolutionary trees in phylodynamics. A curious feature of such models is that they exhibit fundamental symmetries when the birth and death rates are interchanged. In this paper, we explain and formally derive these transformational symmetries. We also show that these transformational symmetries (encoded in algebraic identities) are preserved even when taxa at the present are sampled with some probability. However, these extended symmetries require the death rate parameter to sometimes take a negative value. In the last part of this paper, we describe the relevance of these transformations and their application to computational phylodynamics, particularly to maximum likelihood and Bayesian inference methods, as well as to model selection. Phylodynamics, phylogenetics, speciation-extinction models, birth-death models, algebraic symmetries, maximum likelihood, Bayesian inference
Bee and floral traits affect the characteristics of the vibrations experienced by flowers during buzz-pollination
Authors: Arroyo-Correa Blanca , Beattie Ceit Elisabeth , Vallejo-Marin Mario
Published: December 2018

During buzz pollination, bees use their indirect flight muscles to produce vibrations that are transmitted to the flowers and result in pollen release. Although buzz pollination has been known for >100 years, we are still in the early stages of understanding how bee and floral characteristics affect the production and transmission of floral vibrations. Here we analysed floral vibrations produced by four closely related bumblebee taxa (Bombus spp.) on two buzz-pollinated plants species (Solanum spp.). We measured floral vibrations transmitted to the flower to establish the extent to which the mechanical properties of floral vibrations depend on bee and plant characteristics. By comparing four bee taxa visiting the same plant species, we found that peak acceleration (PA), root mean-squared acceleration (RMS) and frequency varies between bee taxa, but that neither bee size (intertegular distance) or flower biomass (dry weight) affect PA, RMS or frequency. A comparison of floral vibrations of two bee taxa visiting flowers of two plant species, showed that, while bee species affects PA, RMS and frequency, plant species affects acceleration (PA and RMS) but not frequency. When accounting for differences in the transmission of vibrations across the two types of flowers, using a species-specific 'coupling factor', we found that RMS acceleration and peak displacement does not differ between plant species. This suggests that bees produce the same initial acceleration in different plants but that transmission of these vibrations through the flower is affected by floral characteristics.
Cheaters shape the evolution of phenotypic heterogeneity in Bacillus subtilis biofilms
Authors: Martin Marivic , Dragoš Anna , Otto Simon B. , Schäfer Daniel , Brix Susanne , Maróti Gergely , Kovács Ákos T.
Published: December 2018

Biofilms are closely packed cells held and shielded by extracellular matrix composed of structural proteins and exopolysaccharides (EPS). As matrix components are costly to produce and shared within the population, EPS-deficient cells can act as cheaters by gaining benefits from the cooperative nature of EPS producers. Remarkably, genetically programmed EPS producers can also exhibit phenotypic heterogeneity at single cell level. Previous studies have shown that spatial structure of biofilms limits the spread of cheaters, but the long-term influence of cheating on biofilm evolution is not well understood. Here, we examine the influence of EPS non-producers on evolution of matrix production within the populations of EPS producers in a model biofilm-forming bacterium, Bacillus subtilis. We discovered that general adaptation to biofilm lifestyle leads to an increase in phenotypical heterogeneity of eps expression. Apparently, prolonged exposure to EPS-deficient cheaters, may result in different adaptive strategy, where eps expression increases uniformly within the population. We propose a molecular mechanism behind such adaptive strategy and demonstrate how it can benefit the EPS-producers in the presence of cheaters. This study provides additional insights on how biofilms adapt and respond to stress caused by exploitation in long-term scenario.
Consistent alterations of human fecal microbes after transplanted to germ-free mice
Authors: Li Yanze , Cao Wenming , Gao Na L , Zhao Xing-Ming , Chen Wei-Hua
Published: December 2018

Background

Fecal microbiota transplant (FMT) of human fecal samples to germ-free (GF) mice is useful for establishing causal relationships between gut microbiota and human phenotypes. However, due to intrinsic differences between human and mouse intestines and distinct diets between the two organisms, replicating human phenotypes in mouse through FMT is not guaranteed; similarly, treatments that are effective in mouse models do not guarantee their success in human either.

Results

In this study, we aimed to identify human gut microbes that have undergone significant and consistent changes after transplanted to GF mice across multiple experimental settings. By comparing gut microbiota profiles in 1,713 human-mouse pairs, we found strikingly on average <50% of the human gut microbes can be re-established in mice at the species level; among which, more than 1/3 have undergone significant changes (referred as to “variable microbes”), most of which were consistent across multiple human-mouse pairs and experimental settings. Consistently, one-third of human samples had changed their enterotypes, i.e. significant changes in their leading species after FMT. Mice fed with controlled diet showed significant decrease in the enterotype change rate (~25%) as compared those with non-controlled diet (~50%), suggesting a possible solution for rescue. Strikingly, most of the variable microbes have been implicated in human diseases, with some being recognized as causing species.

Conclusions

Our results highlighted the challenges of using mouse model in replicating human gut microbiota-associated phenotypes, provided useful information for researchers using mice in their gut microbiota studies and call for additional validations after FMT.
ECT2 associated to PRICKLE1 are poor-prognosis markers in triple-negative breast cancer
Authors: Daulat Avais M. , Finetti Pascal , Revinski Diego , Wagner Mônica Silveira , Camoin Luc , Audebert Stéphane , Birnbaum Daniel , Kodjabachian Laurent , Borg Jean-Paul , Bertucci François
Published: December 2018

Background

Triple-negative breast cancers are poor-prognosis tumors characterized by absence of molecular signature and are chemotherapy is still the only systemic treatment. Currently, research focus to identify biomarkers that may be usable for prognosis and/or for treatment, notably among the proteins involved in cell migration and metastatic capacity.

Methods

We used proteomic approach to identify protein complexes associated to PRICKLE1 and the mRNA expression level of the corresponding genes in a retrospective series of 8,982 clinically annotated patients with invasive primary breast cancer were assessed. Then, we characterize molecularly the interaction between PRICKLE1 and the guanine nucleotide exchange factor ECT2. Finally, experiments in Xenopus have been carrying out to determine their evolutionary conserved interaction.

Results

We have identified a network of proteins interacting with the prometastatic scaffold protein PRICKLE1 that includes several small G-protein regulators involved in cell migration and metastasis. Combined analysis expression of PRICKLE1 and small G-protein regulators expression has a strong prognostic value in TNBC. We show that PRICKLE1 controls the activity of ECT2 on RAC1 signaling, a pathway required for cancer cell dissemination.

Conclusions

This work supports the idea that promigratory proteins, which are overexpressed in cancerous epithelium, are suitable pharmaceutical targets.
Evolution of regulatory networks associated with traits under selection in cichlids
Authors: Mehta Tarang K. , Koch Christopher , Nash Will , Knaack Sara A. , Sudhakar Padhmanand , Olbei Marton , Bastkowski Sarah , Penso-Dolfin Luca , Korcsmaros Tamas , Haerty Wilfried , Roy Sushmita , Di-Palma Federica
Published: December 2018

Seminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is still known about gene regulatory network (GRN) evolution associated with phenotypic effect across ecologically-diverse species. Using a novel approach to reconstruct GRNs in vertebrate species, we aimed to study GRN evolution in representative species of the most striking example of an adaptive radiation, the East African cichlids. We previously demonstrated how the explosive phenotypic diversification of East African cichlids is attributed to diverse molecular mechanisms, including accelerated regulatory sequence evolution and gene expression divergence. To investigate these mechanisms across species at a genome-wide scale, our novel network-based approach identifies ancestral and extant gene co-expression modules along a phylogeny, and by integrating associated regulators, predicts candidate regulatory regions implicated in traits under selection in cichlids. As a case study, we present data from a well-studied adaptive trait - the visual system - for which we report striking cases of network rewiring for visual opsin genes, identify discrete regulatory variants, and investigate the plausibility of their association with cichlid visual system evolution. In regulatory regions of visual opsin genes,in vitroassays confirm that transcription factor binding site mutations disrupt regulatory edges across species, and segregate according to lake species phylogeny and ecology, suggesting GRN rewiring in radiating cichlids. Our approach revealed numerous novel potential candidate regulatory regions across cichlid genomes with no prior association, as well as those with previously reported associations to known adaptive evolutionary traits, thus providing proof of concept.
Can a flux-based mechanism explain positioning of protein clusters in a three-dimensional cell geometry?
Authors: Kober Matthias , Bergeler Silke , Frey Erwin
Published: December 2018

The plane of bacterial cell division must be precisely positioned. In the bacterium Myxococcus xanthus, the proteins PomX and PomY form a large cluster, which is tethered to the nucleoid by the ATPase PomZ and moves in a stochastic, but biased manner towards midcell, where it initiates cell division. Previously, a positioning mechanism based on the fluxes of PomZ on the nucleoid was proposed. However, the cluster dynamics was analyzed in a reduced, one-dimensional geometry. Here we introduce a mathematical model that accounts for the three-dimensional shape of the nucleoid, such that nucleoid-bound PomZ dimers can diffuse past the cluster without interacting with it. Using stochastic simulations, we find that the cluster still moves to and localizes at midcell. Redistribution of PomZ by diffusion in the cytosol is essential for this cluster dynamics. Our mechanism also positions two clusters equidistantly on the nucleoid. We conclude that a flux-based mechanism allows for cluster positioning in a biologically realistic three-dimensional cell geometry.
Proteome Integral Stability Alteration assay dramatically increases throughput and sensitivity in profiling factor-induced proteome changes
Authors: Gaetani Massimiliano , Sabatier Pierre , Saei Amir Ata , Beusch Christian , Yang Zhe , Lundstrom Susanna , Zubarev Roman A.
Published: December 2018

Various factors, including drugs as well as non-molecular influences, induce alterations in the stability of proteins in cell lysates, living cells and organisms. These alterations can be probed by applying a stability-modifying agent, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or factor intensity can be used. However, the corresponding analysis scheme has a low throughput and high cost. Additionally, since traditional data analysis employs curve fitting, proteins with unusual behavior are frequently ignored. The novel Proteome Integral Stability Alteration (PISA) assay avoids these issues altogether, increasing the analysis throughput by one to two orders of magnitude for unlimited number of parameter variation points. The consumption of the compound and biological material decreases by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.