bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Policy and Food Security in Ethiopia
Authors: Johnston Deborah , Walls Helen
Published: February 2019

Ethiopia has an integrated approach to addressing nutrition. However, greater clarity is needed on the wider impact of policy on food and nutrition. We focus on the interrelationship between economic policy and nutrition policy (defined as including all food- and nutrition-relevant policy). While Ethiopia’s policy has had notable successes, particularly with addressing stunting, two key challenges remain. First, some indicators such as wasting and anaemia in children under five have shown far less improvement. Second, the bottom quintile of children has seen far more limited general improvement than the population as a whole. We argue that the focus of government policy needs to shift from food availability to broader issues of food acquisition and particularly food affordability, which is mediated through food prices and waged employment. Of particular concern is the rising price of animal-source products and other non-staple foods, which may be related to the challenges of addressing some nutritional indicators.
Education and Economic Development in Ethiopia, 1991–2017
Authors: Rekiso Zinabu Samaro
Published: February 2019

This chapter critically examines the major achievements and challenges of the education sector in Ethiopia between 1991 and 2017 from the perspective of long-term economic development and structural transformation. The chapter finds that Ethiopia has achieved enormous success in terms of increasing access to all levels of education throughout the country but the achievement has been at the cost of a vicious cycle of low education quality. In addition, the chapter argues that failure to significantly change the productive structure of the economy has resulted in persistently high levels of unemployment, underemployment, and brain drain of the better-educated human resources of the country. The chapter concludes that there is a need for synergistic, dynamic, context-specific, and comprehensive policies and strategies aimed at progressively moving the Ethiopian economy away from its current specialization in nature-intensive, low-skill, low-knowledge, low-technology economic activities towards ‘mind-intensive’, higher-skill, and technology-intensive economic activities.
Agricultural Markets in Ethiopia
Authors: Minten Bart , Reardon Thomas , Tamru Seneshaw
Published: February 2019

Ethiopia’s agricultural markets are quickly evolving, driven by major contextual changes including high population growth, rapid urbanization, major infrastructure investments, income growth, diet change, and policy reform. Agricultural supply chains are rapidly growing, and they are an increasing source of employment in the country. Agricultural markets are found to be better integrated and marketing margins and seasonal price amplitudes to have become smaller over time, but we also see an increase in prices of nutritious high-value foods, and this is in contrast to staple cereal prices. Although food imports and the number of food aid beneficiaries have not reduced over time, Ethiopia remained a net agricultural exporter, in value terms, for all but one year in the decade before this study, illustrating at the national level the relatively good performance of the agricultural sector.
The Ethiopian Manufacturing Sector Productivity, Export, and Competitiveness
Authors: Shiferaw Admasu , Söderbom Måns
Published: February 2019

Over the last two decades the Ethiopian manufacturing sector has experienced rapid expansion in terms of the number of firms, sales, and employment. This chapter examines the performance of the manufacturing sector using aggregate data and firm-level panel data compiled by the Central Statistical Agency (CSA) of Ethiopia. The focus is on three dimensions of performance: productivity growth, the extent of export orientation, and the competitiveness of domestic firms in the global context. Manufacturing remains a relatively small sector in terms of contribution to GDP and employment, and it has yet to become export oriented even by African standards. In examining productivity growth, the analysis addresses within-firm productivity growth and its heterogeneity across firms, as well as the role of resource reallocation from less efficient firms to more efficient ones.
Technological Learning and Industrialization in Ethiopia
Authors: Tesfachew Taffere
Published: February 2019

Ethiopia has been one of the world’s fastest-growing economies since 2003. This success has been achieved largely through public investment in infrastructure and agricultural productivity. Building on these accomplishments, the country has embarked on an ambitious programme of export-led industrialization anchored in the manufacturing sector. An important prerequisite for success is the ability of countries and their firms to engage in constant technological learning and to acquire new technologies—technologies essential to the production and export of high-quality products. This chapter reviews the process of technological learning and upgrading in Ethiopia and assesses whether the country is accumulating the technological capability needed for export-led growth. It argues that while recent growth has generated momentum for knowledge accumulation, the gap with competitor countries remains wide. It also identifies the main channels and drivers of technology transfer and technological learning in Ethiopia. Trade and FDI are singled out as crucial.
Ethiopia’s Constitutional Framework and Legal Institutions for Development
Authors: Fikre Belachew Mekuria , Tadesse Menberetsehai
Published: February 2019

Though one of the key organizing principles that underpin the current constitution is the creation of a single economic community, the country’s long history of legal transplantation does not necessarily complement this aspiration. This chapter examines how the state-managed developmental enterprise continuously negotiates with the rather ‘foreign’ legal elements, usually to the former’s detriment. The chapter takes a closer look at some of the key elements of the constitution and legal institutions vital for economic growth. Ethiopia’s federal state system together with the developmental state approach can only positively contribute to the creation of a single economic community when some of the key areas in the country’s legal development are revisited to align with its economic development model. The various areas examined in this work demonstrate the dilemmas faced when using law as instrument to achieve economic progress under the developmental state policy of the government in power.
Three Sectoral Policies in Ethiopia’s Structural Transformation
Authors: Lopes Carlos
Published: February 2019

Ethiopia’s stellar growth performance, guided by amicable development planning, has created a common and shared agenda for economic transformation that has fostered better social outcomes in poverty, universal education, child health, and combating AIDS. This chapter attempts to explore the interest and fascination surrounding the Ethiopian development path, beginning with a consideration of the policy innovations that underpin the experience. It identifies the similarities that connect lessons from three disparate sectoral perspectives—industrialization, social protection/food security, and the success story of Ethiopian Airlines—underlining the pivotal role of coherence, ambition, and innovation in Ethiopia’s development trajectory. Central to these characteristics is the notion that structural transformation is an aggregate of socio-economic sector successes and its potential replicability by other African countries.
Constraints on the Ethiopian Floriculture Industry
Authors: Melese Ayelech T.
Published: February 2019

The abilities of domestic firms to expand their business into high-productivity sectors and the effects of employment in productive industries are regarded as a challenge to Ethiopia’s structural transformation efforts. The experience of the Ethiopian floriculture industry shows that many domestic firms collapsed after an early burst of firm creation. Fifteen remaining firms, with varying capability levels, appear to be struggling to expand their business and to move up the technological ladder. This chapter identifies the major areas where the domestic firms lack capability and the factors that are weakening them, including the high labour turnover prevalent across the sector. The sector has created widespread employment, predominantly for women, but its impact on worker well-being is limited. These factors imply a weak contribution by the sector to the virtuous cycle of investment, productivity, and employment that is needed to expand productive capabilities, reduce poverty, and challenge gender inequality.
The Value of Offshore Secrets: Evidence from the Panama Papers
Authors: O’Donovan James , Wagner Hannes F , Zeume Stefan
Published: February 2019

We exploit one of the largest data leaks, to date, to study whether and how firms use secret offshore vehicles. From the leaked data, we identify 338 listed firms as users of secret offshore vehicles and document that these vehicles are used to finance corruption, avoid taxes, and expropriate shareholders. Overall, the leak erased $\$$174 billion in market capitalization among implicated firms. Following the increased transparency brought about by the leak, implicated firms experience lower sales from perceptively corrupt countries and avoid less tax. We conservatively estimate that 1 in 7 firms have offshore secrets.

Received May 29, 2017; editorial decision December 2, 2018 by Editor Itay Goldstein. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Managing Fusarium Head Blight in Winter Barley With Cultivar Resistance and Fungicide
Authors: Cowger Christina , Arellano Consuelo , Marshall David , Fitzgerald Joshua
Published: February 2019

Although there has been research on managing Fusarium head blight (FHB) in spring barley, little has been published on cultivar resistance and optimal fungicide timing for FHB management in winter barley. A 3-year (2015 to 2017) field experiment was conducted to measure FHB resistance of winter barley varieties, gauge the potential benefit from a fungicide, and help determine the optimal timing for fungicide application. The split-plot experiment took place in a misted, inoculated nursery in Raleigh, North Carolina using main plots of four winter barley cultivars (Atlantic, Endeavor, Nomini, and Thoroughbred). Three fungicide treatments were applied to subplots: prothioconazole + tebuconazole at full spike emergence, the same fungicide 6 days later, or no fungicide. The late applications significantly reduced FHB index in each of 3 years and significantly reduced deoxynivalenol (DON) in harvested grain in 2 of the 3 years. Applications at full spike emergence also yielded significant benefit in 1 of the 3 years for each parameter. Neither disease symptoms nor DON gave reason to prefer one of the fungicide timings over the other. Across the 3 years, DON ranked the cultivars Endeavor < Nomini = Thoroughbred < Atlantic. Combining the moderate resistance of Endeavor with a fungicide application and averaging the two timings resulted in a 75% DON reduction compared with unsprayed Atlantic. Taken together, our results indicate that barley growers concerned about minimizing DON should both plant moderately resistant varieties and apply fungicide if there is scab risk. During the same period, 16 commercial winter barley cultivars were tested in from three to seven Virginia and North Carolina environments each, and the DON results were compared after standardization across environments. The winter two-row malting barley cultivars Endeavor and Calypso displayed superior and robust DON resistance across environments.
The coevolutionary biology of brood parasitism: a call for integration
Authors: Thorogood Rose , Spottiswoode Claire N. , Portugal Steven J. , Gloag Ros
Published: February 2019

Obligate brood-parasitic cheats have fascinated natural historians since ancient times. Passing on the costs of parental care to others occurs widely in birds, insects and fish, and often exerts selection pressure on hosts that in turn evolve defences. Brood parasites have therefore provided an illuminating system for researching coevolution. Nevertheless, much remains unknown about how ecology and evolutionary history constrain or facilitate brood parasitism, or the mechanisms that shape or respond to selection. In this special issue, we bring together examples from across the animal kingdom to illustrate the diverse ways in which recent research is addressing these gaps. This special issue also considers how research on brood parasitism may benefit from, and in turn inform, related fields such as social evolution and immunity. Here, we argue that progress in our understanding of coevolution would benefit from the increased integration of ideas across taxonomic boundaries and across Tinbergen’s Four Questions: mechanism, ontogeny, function and phylogeny of brood parasitism. We also encourage renewed vigour in uncovering the natural history of the majority of the world's brood parasites that remain little-known. Indeed, it seems very likely that some of nature’s brood parasites remain entirely unknown, because otherwise we are left with a puzzle: if parental care is so costly, why is brood parasitism not more common?

This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
Under the radar: detection avoidance in brood parasitic bees
Authors: Litman Jessica R.
Published: February 2019

Brood parasitism is a specialized form of parasitism in which the offspring of a parasite develops on the food provisions gathered by a host species for its own young. Obligate brood parasitic lineages have lost the ability to acquire provisions for their young and thus rely entirely on the location of an appropriate host to serve as a food-provider. Solitary bees provide some of the most fascinating examples of brood parasitism in animals. Most solitary bees build and provision their own nests. Some, however, usurp the nests of other species of bees. These brood parasites, or ‘cuckoo’ bees, deposit their eggs on the pollen provisions collected by a host bee for her own offspring. The provisions stored by the host bee are not sufficient to sustain the development of both the host's larva and that of the brood parasite and the parasite must kill the offspring of its host in order to obtain enough nourishment to complete its development. As a consequence, there is fierce competition between the host bee seeking to protect her nest from attack and the brood parasite seeking to avoid detection by the host in order to successfully deposit her eggs in an appropriate nest. In this paper, I review the behaviours that allow brood parasitic bees to escape detection by their hosts. Identifying these behaviours, and placing them within the general context of strategies employed by brood parasitic bees to parasitize the nests of their hosts, is key to understanding how brood parasitic lineages may have evolved from nest-building ancestors, decrypting the selective pressures that drive evolutionary transitions from one strategy to another and, more broadly, revealing how similar selective pressures in widely divergent lineages of animals have given rise to remarkably convergent behaviours.

This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
The brood parasite's guide to inclusive fitness theory
Authors: Gloag Ros , Beekman Madeleine
Published: February 2019

Hamilton's theory of inclusive fitness provides a framework for understanding the evolution of social behaviour between kin, including parental and alloparental care. Brood parasitism is a reproductive tactic in which parasites exploit the care of other individuals of the same species (conspecific parasitism) or different species (interspecific parasitism) to rear their brood. Here, drawing from examples in birds and social insects, we identify two insights into brood parasitism that stem from inclusive fitness theory. First, the kin structure within nests, or between neighbouring nests, can create a niche space favouring the evolution of conspecific parasitism. For example, low average relatedness within social insect nests can increase selection for reproductive cheats. Likewise, high average relatedness between adjacent nests of some birds can increase a female's tolerance of parasitism by her neighbour. Second, intrabrood conflict will be high in parasitized broods, from the perspective of both parasite and host young, relative to unparasitized broods. We also discuss offspring recognition by hosts as an example of discrimination in a kin-selected social behaviour. We conclude that the inclusive fitness framework is instructive for understanding aspects of brood parasite and host evolution. In turn, brood parasites present some unique opportunities to test the predictions of inclusive fitness theory.

This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
Monogamy without parental care? Social and genetic mating systems of avian brood parasites
Authors: Feeney William E. , Riehl Christina
Published: February 2019

Classic evolutionary theory predicts that monogamy should be intimately linked with parental care. It has long been assumed, therefore, that avian brood parasites—which lay their eggs in the nests of ‘host’ species and provide little, if any, parental care—should be overwhelmingly promiscuous. However, recent studies have revealed that the social mating systems of brood parasites are surprisingly diverse, encompassing lek polygyny, monogamy, polygamy and promiscuity. What ecological or phylogenetic factors explain this variation, and why are some brood parasites apparently monogamous? Here we review the social and genetic mating systems of all 75 brood parasitic species for which data are available and evaluate several hypotheses that may help explain these patterns. We find that social monogamy is widespread, often co-occurring with territoriality and cooperative behaviour by the mated pair. Comparative studies, though preliminary, suggest that in some species, monogamy is associated with low host density and polygamy with higher host density. Interestingly, molecular data show that genetic and social mating systems can be entirely decoupled: genetic monogamy can occur in parasitic species that lack behavioural pair-bonds, possibly as a by-product of territoriality; conversely, social monogamy has been reported in parasites that are genetically polygamous. This synthesis suggests that social and genetic monogamy may result from very different selective pressures, and that male–female cooperative behaviours, population density and territoriality may all interact to favour the evolution of monogamous mating in brood parasites. Given that detailed descriptive data of social, and especially genetic, mating systems are still lacking for the majority of brood parasitic species, definitive tests of these hypotheses await future work.

This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
Early life-history features associated with brood parasitism in the cuckoo catfish,Synodontis multipunctatus(Siluriformes: Mochokidae)
Authors: Cohen Marcus S. , Hawkins M. Brent , Stock David W. , Cruz Alexander
Published: February 2019

The cuckoo catfish,Synodontis multipunctatus, is the only known obligate brood parasite among fishes, exploiting the parental care of mouthbrooding cichlids endemic to Lake Tanganyika. Comparisons of this system to brood parasitism in birds may reveal broader principles that underlie the evolution of this life-history strategy in vertebrates. However, little is known about the features of the cuckoo catfish that enable this species to successfully parasitize cichlids. Here, we examine early ontogeny of the cuckoo catfish and compare it to that of its cichlid hosts as well as a non-parasitic congener. We found that cuckoo catfish embryos develop and hatch in advance of host embryos, and begin feeding on cichlid young just as they start to hatch. Overall timing of ontogeny in the cuckoo catfish was found to be similar to that of the substrate-spawning congenerSynodontis lucipinnis, suggesting that more rapid development of the cuckoo catfish relative to cichlids is not a unique adaptation to brood parasitism. However, we found that cuckoo catfish progeny exhibit extensive morphological differences fromS.lucipinnis, which may represent adaptations to brood parasitism. These life-history observations reveal both similarities and differences between the cuckoo catfish system and brood parasitism in other lineages.

This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
Vive la difference! Self/non-self recognition and the evolution of signatures of identity in arms races with parasites
Authors: Spottiswoode Claire N. , Busch Robert
Published: February 2019

In arms races with parasites, hosts can evolve defences exhibiting extensive variability within populations, which signals individual identity (‘signatures’). However, few such systems have evolved, suggesting that the conditions for their evolution are uncommon. We review (a) polymorphic egg markings that allow hosts of brood-parasitic birds to recognize and reject parasitic eggs, and (b) polymorphic tissue antigens encoded in the major histocompatibility complex (MHC), which present self- and pathogen-derived peptides to T cells of the immune system. Despite the profound differences between these systems, they share analogous features: (i) self/non-self discrimination by a highly specific recognition system (bird eyes and T-cell antigen receptor, respectively), which antagonists may escape by evolving evasion or mimicry; (ii) a self substrate upon which diversifying selection can act (eggs, and MHC molecules); (iii) acquired knowledge of self (resulting in acceptance of own eggs, and immune tolerance); and (iv) fitness costs associated with attack on self or lack of parasite detection. We suggest that these features comprise a set of requirements for parasites to drive the evolution of identity signatures in hosts, which diminish the likelihood of recognition errors. This may help to explain the variety of trajectories arising from arms races in different antagonistic contexts.

This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
Very rapid flow cytometric assessment of antimicrobial susceptibility during the apparent lag phase of microbial (re)growth
Authors: Jindal Srijan , Thampy Harish , Day Philip J. R. , Kell Douglas B.
Published: February 2019

Rapid changes in the number and flow cytometric behaviour of cells of

E. coli

taken from a stationary phase and inoculated into rich medium.
VAMPr: VAriant Mapping and Prediction of antibiotic resistance via explainable features and machine learning
Authors: Kim Jiwoong , Greenberg David E , Pifer Reed , Jiang Shuang , Xiao Guanghua , Shelburne Samuel A , Koh Andrew , Xie Yang , Zhan Xiaowei
Published: February 2019

Antimicrobial resistance (AMR) is an increasing threat to public health. Current methods of determining AMR rely on inefficient phenotypic approaches, and there remains incomplete understanding of AMR mechanisms for many pathogen-antimicrobial combinations. Given the rapid, ongoing increase in availability of high density genomic data for a diverse array of bacteria, development of algorithms that could utilize genomic information to predict phenotype could both be useful clinically and assist with discovery of heretofore unrecognized AMR pathways. To facilitate understanding of the connections between DNA variation and phenotypic AMR, we developed a new bioinformatics tool, variant mapping and prediction of antibiotic resistance (VAMPr), to (1) derive gene ortholog-based sequence features for variants; (2) interrogate these explainable gene-level variants for their known or novel associations with AMR; and (3) build accurate models to predict AMR based on whole genome sequencing data. Following the Clinical & Laboratory Standards Institute (CLSI) guidelines, we curated the publicly available sequencing data for 3,393 bacterial isolates from 9 species along with AMR phenotypes for 29 antibiotics. We detected 14,615 variant genotypes and built 93 association and prediction models. The association models confirmed known genetic antibiotic resistance mechanisms, such as blaKPC and carbapenem resistance consistent with the accurate nature of our approach. The prediction models achieved high accuracies (mean accuracy of 91.1% for all antibiotic-pathogen combinations) internally through nested cross validation and were also validated using external clinical datasets. The VAMPr variant detection method, association and prediction models will be valuable tools for AMR research for basic scientists with potential for clinical applicability.
Optical measurement of voltage sensing by endogenous ion channels
Authors: Thapa Parashar , Stewart Robert , Sepela Rebecka J. , Vivas Oscar , Parajuli Laxmi K. , Lillya Mark , Fletcher-Taylor Sebastian , Cohen Bruce E. , Zito Karen , Sack Jon T.
Published: February 2019

A primary goal of molecular physiology is to understand how conformational changes of proteins affect the function of cells, tissues, and organisms. Here, we describe an imaging method for measuring the conformational changes of the voltage sensors of endogenous ion channel proteins within live tissue, without genetic modification. We synthesized GxTX-594, a variant of the peptidyl tarantula toxin guangxitoxin-1E, conjugated to a fluorophore optimal for two-photon excitation imaging through light-scattering tissue. GxTX-594 targets the voltage sensors of Kv2 proteins, which form potassium channels and plasma membrane–endoplasmic reticulum junctions. GxTX-594 dynamically labels Kv2 proteins on cell surfaces in response to voltage stimulation. To interpret dynamic changes in labeling intensity, we developed a statistical thermodynamic model that relates the conformational changes of Kv2 voltage sensors to labeling intensity. We used two-photon excitation imaging of rat brain slices to image Kv2 proteins in neurons. This imaging method enabled identification of conformational changes of endogenous Kv2 voltage sensors in tissue.
Tissue structure accelerates evolution: premalignant sweeps precede neutral expansion
Authors: West Jeffrey , Schenck Ryan O. , Gatenbee Chandler , Robertson-Tessi Mark , Anderson Alexander R. A.
Published: February 2019

Cancer has been hypothesized to be a caricature of the renewal process of the tissue of origin: arising from (and maintained by) small subpopulations capable of continuous growth1. The strong influence of the tissue structure has been convincingly demonstrated in intestinal cancers where adenomas grow by the fission of stem-cell-maintained glands influenced by early expression of abnormal cell mobility in cancer progenitors2, 3. So-called “born to be bad” tumors arise from progenitors which may already possess the necessary driver mutations for malignancy4, 5and metastasis6. These tumors subsequently evolve neutrally, thereby maximizing intratumoral heterogeneity and increasing the probability of therapeutic resistance. These findings have been nuanced by the advent of multi-region sequencing, which uses spatial and temporal patterns of genetic variation among competing tumor cell populations to shed light on the mode of tumor evolution (neutral or Darwinian) and also the tempo4, 7–11. Using a classic, well-studied model of tumor evolution (a passenger-driver mutation model12–16) we systematically alter spatial constraints and cell mixing rates to show how tissue structure influences functional (driver) mutations and genetic heterogeneity over time. This model approach explores a key mechanism behind both inter-patient and intratumoral tumor heterogeneity: competition for space. Initial spatial constraints determine the emergent mode of evolution (neutral to Darwinian) without a change in cell-specific mutation rate or fitness effects. Transition from early Darwinian to late neutral evolution is accelerated by the combination of two factors: spatial constraints and well-timed dispersal events.
InterLig: a fast and accurate software for ligand-based virtual screening
Authors: Mirabello Claudio , Wallner Björn
Published: February 2019

In the past few years, drug discovery processes have been relying more and more on computational methods to sift out the most promising molecules before time and resources are spent to test them in experimental settings. Whenever the protein target of a given disease is not known, it becomes fundamental to have accurate methods for ligand-based Virtual Screening, which compare known active molecules against vast libraries of candidate compounds. Recently, 3D-based similarity methods have been developed that are capable of scaffold-hopping and to superimpose matching molecules. Here, we present InterLig, a new method for the comparison and superposition of small molecules based on 3D, topologically-independent alignments of atoms. We test InterLig on a standard benchmark and show that it compares favorably to the best currently available 3D methods.

InterLig is open source and is available to everyone at: http://wallnerlab.org/interlig.
SIMON, an automated machine learning system reveals immune signatures of influenza vaccine responses
Authors: Tomic Adriana , Tomic Ivan , Rosenberg-Hasson Yael , Dekker Cornelia L. , Maecker Holden T. , Davis Mark M.
Published: February 2019

Machine learning holds considerable promise for understanding complex biological processes such as vaccine responses. Capturing interindividual variability is essential to increase the statistical power necessary for building more accurate predictive models. However, available approaches have difficulty coping with incomplete datasets which is often the case when combining studies. Additionally, there are hundreds of algorithms available and no simple way to find the optimal one. Here, we developed Sequential Iterative Modelling “OverNight” or SIMON, an automated machine learning system that compares results from 128 different algorithms and is particularly suitable for datasets containing many missing values. We applied SIMON to data from five clinical studies of seasonal influenza vaccination. The results reveal previously unrecognized CD4+and CD8+T cell subsets strongly associated with a robust antibody response to influenza antigens. These results demonstrate that SIMON can greatly speed up the choice of analysis modalities. Hence, it is a highly useful approach for data-driven hypothesis generation from disparate clinical datasets. Our strategy could be used to gain biological insight from ever-expanding heterogeneous datasets that are publicly available.
Subject sex and partner sex modulate social touch responses across multiple cortical areas
Authors: Ebbesen Christian L. , Bobrov Evgeny , Rao Rajnish P. , Brecht Michael
Published: February 2019

Touch is a fundamental aspect of mammalian social, parental and sexual behavior. Human affective touch is critical for healthy child development and shows great promise as a novel therapeutic strategy for mental disorders characterized by social dysfunction, such as anxiety, depression and autism spectrum disorder. However, despite our detailed knowledge about cortical processing of non-social touch, we still know very little about how social touch modulates cortical circuits. We investigated the activity patterns of single neurons (N = 1156) across five sensory and frontal cortical areas in both male and female rats (N = 28) engaging in naturalistic social facial touch with male and female conspecifics. We found that information about social touch is widely available across cortex. Besides touch, the sex of the interaction partner (a biologically significant feature) is a major determinant of single neuron activity, and across cortex we observed 25.7% ‘touch’ and 11.9% ‘sex-touch’ responses. Although all areas investigated had access to social touch and partner sex information, social touch modulated different cortical areas in different ways. Finally, we found that network activity patterns during social touch depend on both subject sex and partner sex. Interestingly, these sex-differences in network activity patterns were differences in response magnitude and would not be evident without single cell resolution. Our observations suggest that socio-sexual characteristics of touch (subject and partner sex) widely modulate cortical activity and need to be investigated with cellular resolution.
Design and evaluation of novel 4-anilinoquinolines and quinazolines EGFR inhibitors in lung cancer and chordoma
Authors: Asquith Christopher R. M. , Maffuid Kaitlyn A. , Laitinen Tuomo , Torrice Chad D. , Tizzard Graham J. , Alamillo-Ferrer Carla , Koshlap Karl M. , Crona Daniel J. , Zuercher William J.
Published: February 2019

Epidermal growth factor receptor (EGFR) inhibitors have been used to target non-small cell lung cancer (NSCLC) and chordomas with varying amounts of success. We have probed several key structural features including an interaction with Asp855 within the EGFR DGF motif and interactions with the active site water network. The EGFR target engagement was then evaluated in an in-cell assay. Additionally, inhibitors were profiled in representative cellular models of NSCLC and chordomas. In addition to a structure activity relationship insights for EGFR inhibtior design, we also identified a compound (18) that is the most potent inhibitor (IC50 = 310 nM) on the UCH-2 chordoma cell line to date.
Cusp-artifacts in high order Superresolution Optical Fluctuation Imaging
Authors: Yi Xiyu , Weiss Shimon
Published: February 2019

Superresolution Optical Fluctuation Imaging (SOFI) offers a simple and affordable alternative to the more sophisticated (and expensive) super-resolution imaging techniques such as STED, PALM, STORM, structured illumination, and other derivative methods. In SOFI, the calculation of high order cumulants provides higher resolution but drastically expands the dynamic range of the resulting image. In this study, we have identified another type of artifact for high order SOFI cumulants, dubbed as ‘cusp artifacts.’ A series of realistic simulations are performed to study the cusp artifacts under the influences of various factors, including the blinking statistics, the spatial distribution of photophysical properties of the sample, the total number of frames processed per dataset, photobleaching, and noise. Experiments, simulations, and theory all show that high order cumulants and odd-order moments could suffer from cusp artifacts. These cusp artifacts also degrade the fidelity of bSOFI that has been proposed to solve the dynamic range expansion of image pixel intensities. Alternatively, cusp-artifacts could be altogether eliminated by utilizing even-order moments constructed directly or from cumulants for image reconstruction. Together with dynamic range compression, these approaches yield improved SOFI images. Our study provides new insight into the nature of high order SOFI images, outlines guidelines for developing and screening SOFI-optimized fluorescence probes, and suggests improved strategies for SOFI data acquisition.
Hippocampal Activity Dynamics During Contextual Reward Association in Virtual Reality Place Conditioning
Authors: Williams Sidney B. , Arriaga Moises , Post William W. , Korgaonkar Akshata A. , Morón Jose A. , Han Edward B.
Published: February 2019

Exposure to environmental contexts associated with drug use can induce cravings that promote continued use and/or relapse. Opioid abuse is marked by high relapse rates, suggesting that contextual memories formed during opioid use may be particularly strong. While it is known that reward-seeking behavior is controlled by the mesolimbic reward circuit, little is understood about how contextual memories are altered by drug use. The dorsal hippocampus (dHPC) is necessary for multiple types of contextual learning and the place-specific activity of CA1 place cells map out space in a given environment. Here we examined the neuronal representation of context as animals developed morphine-paired environmental associations using a conditioned place preference (CPP) paradigm. To investigate changes in the hippocampal encoding before, during, and after drug-pairing, we developed a virtual reality (VR) morphine CPP (Mor-CPP) paradigm and used in vivo two-photon calcium imaging to record the activity of CA1 pyramidal neurons. We found increased activity in rewarded contexts following real-time operant conditioning with water rewards, but not after Mor-CPP training, suggesting different neural encoding mechanisms for natural reinforcers and morphine.
In Silico Genetics: Identification of pathogenic nsSNPs in human STAT3 gene associated with Job’s syndrome
Authors: Mustafa Mujahed I. , Abdelmoneim Abdelrahman H. , Elfadol Nafisa M. , Mahmoud Thwayba A. , Hassan Mohamed A.
Published: February 2019

Background

Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job’s syndrome is a rare immunodeficiesncy disease that classically presents in early childhood, characterized by eczematoid dermatitis, characteristic facies, pneumatoceles, hyperextensibility of joints, multiple bone fractures, scoliosis, atopic dermatitis and elevated levels of serum IgE (>2000 IU/ml). The term Autosomal dominant hyper-IgE syndrome has primarily been associated with mutations in STAT3 gene, Located in human chromosome 17q21.

Methods

The human STAT3 gene was investigated in dbSNP/NCBI, 962 SNPs were Homo sapiens; of which 255 were missense SNPs. This selected for in silico analysis by multiple in silico tools to investigate the effect of SNPs on STAT3 protein’s structure and function.

Result

Eleven novel mutations out of 255 nsSNPs that are found to be deleterious effect on the STAT3 structure and function.

Conclusion

A total of eleven novel nsSNPs were predicted to be responsible for the structural and functional modifications of STAT3 protein. The newly recognized genetic cause of the hyper-IgE syndrome affects complex, compartmentalized somatic and immune regulation. This study will opens new doors to facilitate the development of novel diagnostic markers for associated diseases.
Optimal use of statistical methods to validate reference gene stability in longitudinal studies
Authors: Sundaram Venkat Krishnan , Sampathkumar Nirmal Kumar , Massaad Charbel , Grenier Julien
Published: February 2019

Multiple statistical approaches have been proposed to validate reference genes in qPCR assays. However, conflicting results from these statistical methods pose a major hurdle in the choice of the best reference genes. Indeed, as their respective approaches to calculating reference gene stability is different, their suitability has to be tested for a given experimental setting. In this study, the stability of 10 candidate reference genes (Actb, Gapdh, Tbp, Sdha, Pgk1, Ppia, Rpl13a, Hsp60, Mrpl10, Rps26) was assessed using four common statistical approaches (GeNorm, NormFinder, Coefficient of Variation analysis and Pairwise ΔCt method) in a longitudinal setting. We used the development of the cerebellum and the spinal cord of mice as a model to assess the suitability of these statistical methods for reference gene validation. GeNorm and the Pairwise ΔCt were found to be ill suited due to a fundamental assumption in their stability calculations. Whereas, NormFinder and Coefficient of Variation analysis fare better provided they are used complementarily. We therefore devised a workflow combining these two methods for validating reference genes in developmental studies. This workflow proves to be more robust than any of the methods used individually.
Screening for genes that accelerate the epigenetic ageing clock in humans reveals a role for the H3K36 methyltransferase NSD1
Authors: Martin-Herranz Daniel E. , Aref-Eshghi Erfan , Bonder Marc Jan , Stubbs Thomas M. , Stegle Oliver , Sadikovic Bekim , Reik Wolf , Thornton Janet M.
Published: February 2019

Background

Epigenetic clocks are mathematical models that predict the biological age of an individual using DNA methylation data, and which have emerged in the last few years as the most accurate biomarkers of the ageing process. However, little is known about the molecular mechanisms that control the rate of such clocks. Here, we have examined the human epigenetic clock in patients with a variety of developmental disorders, harbouring mutations in proteins of the epigenetic machinery.

Results

Using the Horvath epigenetic clock, we performed an unbiased screen for epigenetic age acceleration (EAA) in the blood of these patients. We demonstrate that loss-of-function mutations in the H3K36 histone methyltransferase NSD1, which cause Sotos syndrome, substantially accelerate epigenetic ageing. Furthermore, we show that the normal ageing process and Sotos syndrome share methylation changes and the genomic context in which they occur. Finally, we found that the Horvath clock CpG sites are characterised by a higher Shannon methylation entropy when compared with the rest of the genome, which is dramatically decreased in Sotos syndrome patients.

Conclusions

These results suggest that the H3K36 methylation machinery is a key component of theepigenetic maintenance systemin humans, which controls the rate of epigenetic ageing, and this role seems to be conserved in model organisms. Our observations provide novel insights into the mechanisms behind the epigenetic ageing clock and we expect will shed light on the different processes that erode the human epigenetic landscape during ageing.
Probabilistic associative learning suffices for learning the temporal structure of multiple sequences
Authors: Martinez Ramon H. , Lansner Anders , Herman Pawel
Published: February 2019

Abstract

Many brain phenomena both at the cognitive and behavior level exhibit remarkable sequential characteristics. While the mechanisms behind the sequential nature of the underlying brain activity are likely multifarious and multi-scale, in this work we attempt to characterize to what degree some of this properties can be explained as a consequence of simple associative learning. To this end, we employ a parsimonious firing-rate attractor network equipped with the Hebbian-like Bayesian Confidence Propagating Neural Network (BCPNN) learning rule relying on synaptic traces with asymmetric temporal characteristics. The proposed network model is able to encode and reproduce temporal aspects of the input, and offers internal control of the recall dynamics by gain modulation. We provide an analytical characterisation of the relationship between the structure of the weight matrix, the dynamical network parameters and the temporal aspects of sequence recall. We also present a computational study of the performance of the system under the effects of noise for an extensive region of the parameter space. Finally, we show how the inclusion of modularity in our network structure facilitates the learning and recall of multiple overlapping sequences even in a noisy regime.
Predicting Pathogenicity of Missense Variants with Weakly Supervised Regression
Authors: Cao Yue , Sun Yuanfei , Karimi Mostafa , Chen Haoran , Moronfoye Oluwaseyi , Shen Yang
Published: February 2019

Quickly growing genetic variation data of unknown clinical significance demand computational methods that can reliably predict clinical phenotypes and deeply unravel molecular mechanisms. On the platform enabled by CAGI (Critical Assessment of Genome Interpretation), we develop a novel “weakly supervised” regression (WSR) model that not only predicts precise clinical significance (probability of pathogenicity) from inexact training annotations (class of pathogenicity) but also infers underlying molecular mechanisms in a variant-specific fashion. Compared to multi-class logistic regression, a representative multi-class classifier, our kernelized WSR improves the performance for the ENIGMA Challenge set from 0.72 to 0.97 in binary AUC (Area Under the receiver operating characteristic Curve) and from 0.64 to 0.80 in ordinal multi-class AUC. WSR model interpretation and protein structural interpretation reach consensus in corroborating the most probable molecular mechanisms by which some pathogenic BRCA1 variants confer clinical significance, namely metal-binding disruption for C44F and C47Y, protein-binding disruption for M18T, and structure destabilization for S1715N.
THINGS: A database of 1,854 object concepts and more than 26,000 naturalistic object images
Authors: Hebart Martin N. , Dickter Adam H. , Kidder Alexis , Kwok Wan Y. , Corriveau Anna , Van Wicklin Caitlin , Baker Chris I.
Published: February 2019

In recent years, the use of a large number of object concepts and naturalistic object images has been growing enormously in cognitive neuroscience research. Classical databases of object concepts are based mostly on a manually-curated set of concepts. Further, databases of naturalistic object images typically consist of single images of objects cropped from their background, or a large number of uncontrolled naturalistic images of varying quality, requiring elaborate manual image curation. Here we provide a set of 1,854 diverse object concepts sampled systematically from concrete picturable and nameable nouns in the American English language. Using these object concepts, we conducted a large-scale web image search to compile a database of 26,107 high-quality naturalistic images of those objects, with 12 or more object images per concept and all images cropped to square size. Using crowdsourcing, we provide higher-level category membership for the 27 most common categories and validate them by relating them to representations in a semantic embedding derived from large text corpora. Finally, by feeding images through a deep convolutional neural network, we demonstrate that they exhibit high selectivity for different object concepts, while at the same time preserving variability of different object images within each concept. Together, the THINGS database provides a rich resource of object concepts and object images and offers a tool for both systematic and large-scale naturalistic research in the fields of psychology, neuroscience, and computer science.
Adapting in larger numbers can increase the vulnerability ofEscherichia colipopulations to environmental changes
Authors: Chavhan Yashraj , Karve Shraddha , Dey Sutirth
Published: February 2019

Larger populations generally adapt faster to their existing environment. However, it is unknown if the population size experienced during evolution influences the ability to face sudden environmental changes. To investigate this issue, we subjected replicateEscherichia colipopulations of different sizes to experimental evolution in an environment containing a cocktail of three antibiotics. In this environment, the ability to actively efflux molecules outside the cell is expected to be a major fitness-affecting trait. We found that all the populations eventually reached similar fitness in the antibiotic cocktail despite adapting at different speeds, with the larger populations adapting faster. Surprisingly, whereas efflux activity enhanced in the smaller populations, it decayed in the larger ones. The evolution of efflux activity was largely shaped by pleiotropic responses to selection and not by drift. This demonstrates that quantitative differences in population size can lead to qualitative differences (decay/enhancement) in the fate of a character during adaptation to identical environments. Furthermore, the larger populations showed inferior fitness upon sudden exposure to several alternative stressful environments. These observations provide a novel link between population size and vulnerability to environmental changes. Counter-intuitively, adapting in larger numbers can render bacterial populations more vulnerable to abrupt environmental changes.