bluuebunny/crossref_metadata_2025_split huggingface dataset:
How urban characteristics affect vulnerability to heat and cold: a multi-country analysis
Authors: Sera Francesco , Armstrong Ben , Tobias Aurelio , Vicedo-Cabrera Ana Maria , Åström Christofer , Bell Michelle L , Chen Bing-Yu , de Sousa Zanotti Stagliorio Coelho Micheline , Matus Correa Patricia , Cruz Julio Cesar , Dang Tran Ngoc , Hurtado-Diaz Magali , Do Van Dung , Forsberg Bertil , Guo Yue Leon , Guo Yuming , Hashizume Masahiro , Honda Yasushi , Iñiguez Carmen , Jaakkola Jouni J K , Kan Haidong , Kim Ho , Lavigne Eric , Michelozzi Paola , Ortega Nicolas Valdes , Osorio Samuel , Pascal Mathilde , Ragettli Martina S , Ryti Niilo R I , Saldiva Paulo Hilario Nascimento , Schwartz Joel , Scortichini Matteo , Seposo Xerxes , Tong Shilu , Zanobetti Antonella , Gasparrini Antonio 
Published: February 2019

AbstractBackgroundThe health burden associated with temperature is expected to increase due to a warming climate. Populations living in cities are likely to be particularly at risk, but the role of urban characteristics in modifying the direct effects of temperature on health is still unclear. In this contribution, we used a multi-country dataset to study effect modification of temperature–mortality relationships by a range of city-specific indicators.MethodsWe collected ambient temperature and mortality daily time-series data for 340 cities in 22 countries, in periods between 1985 and 2014. Standardized measures of demographic, socio-economic, infrastructural and environmental indicators were derived from the Organisation for Economic Co-operation and Development (OECD) Regional and Metropolitan Database. We used distributed lag non-linear and multivariate meta-regression models to estimate fractions of mortality attributable to heat and cold (AF%) in each city, and to evaluate the effect modification of each indicator across cities.ResultsHeat- and cold-related deaths amounted to 0.54% (95% confidence interval: 0.49 to 0.58%) and 6.05% (5.59 to 6.36%) of total deaths, respectively. Several city indicators modify the effect of heat, with a higher mortality impact associated with increases in population density, fine particles (PM2.5), gross domestic product (GDP) and Gini index (a measure of income inequality), whereas higher levels of green spaces were linked with a decreased effect of heat.ConclusionsThis represents the largest study to date assessing the effect modification of temperature–mortality relationships. Evidence from this study can inform public-health interventions and urban planning under various climate-change and urban-development scenarios.
Evolutionary and developmental mismatches are consequences of adaptive developmental plasticity in humans and have implications for later disease risk
Authors: Gluckman Peter D. , Hanson Mark A. , Low Felicia M. 
Published: February 2019

A discrepancy between the phenotype of an individual and that which would confer optimal responses in terms of fitness in an environment is termed ‘mismatch’. Phenotype results from developmental plasticity, conditioned partly by evolutionary history of the species and partly by aspects of the developmental environment. We discuss two categories of such mismatch with reference primarily to nutrition and in the context of evolutionary medicine. The categories operate over very different timescales. A developmental mismatch occurs when the phenotype induced during development encounters a different environment post-development. This may be the result of wider environmental changes, such as nutritional transition between generations, or because maternal malnutrition or placental dysfunction give inaccurate information about the organism's likely future environment. An evolutionary mismatch occurs when there is an evolutionarily novel environment. Developmental plasticity may involve immediate adaptive responses (IARs) to preserve survival if an environmental challenge is severe, and/or predictive adaptive responses (PARs) if the challenge does not threaten survival, but there is a fitness advantage in developing a phenotype that will be better adapted later. PARs can have long-term adverse health consequences if there is a developmental mismatch. For contemporary humans, maternal constraint of fetal growth makes PARs likely even if there is no obvious IAR, and this, coupled with the pervasive nutritionally dense modern environment, can explain the widespread observations of developmental mismatch, particularly in populations undergoing nutritional transition. Both developmental and evolutionary mismatch have important public health consequences and implications for where policy interventions may be most effective.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine'.
The development of individual differences in cooperative behaviour: maternal glucocorticoid hormones alter helping behaviour of offspring in wild meerkats
Authors: Dantzer Ben , Dubuc Constance , Goncalves Ines Braga , Cram Dominic L. , Bennett Nigel C. , Ganswindt Andre , Heistermann Michael , Duncan Chris , Gaynor David , Clutton-Brock Tim H. 
Published: February 2019

The phenotype of parents can have long-lasting effects on the development of offspring as well as on their behaviour, physiology and morphology as adults. In some cases, these changes may increase offspring fitness but, in others, they can elevate parental fitness at a cost to the fitness of their offspring. We show that in Kalahari meerkats (Suricata suricatta), the circulating glucocorticoid (GC) hormones of pregnant females affect the growth and cooperative behaviour of their offspring. We performed a 3-year experiment in wild meerkats to test the hypothesis that GC-mediated maternal effects reduce the potential for offspring to reproduce directly and therefore cause them to exhibit more cooperative behaviour. Daughters (but not sons) born to mothers treated with cortisol during pregnancy grew more slowly early in life and exhibited significantly more of two types of cooperative behaviour (pup rearing and feeding) once they were adults compared to offspring from control mothers. They also had lower measures of GCs as they aged, which could explain the observed increases in cooperative behaviour. Because early life growth is a crucial determinant of fitness in female meerkats, our results indicate that GC-mediated maternal effects may reduce the fitness of offspring, but may elevate parental fitness as a consequence of increasing the cooperative behaviour of their daughters.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Non-genetic inheritance via the male germline in mammals
Authors: Baxter Faye A. , Drake Amanda J. 
Published: February 2019

Numerous studies in humans and in animal models have demonstrated that exposure to adverse environmental conditions in early life results in long-term structural and functional changes in an organism, increasing the risk of cardiometabolic, neurobehavioural and reproductive disorders in later life. Such effects are not limited to the first generation offspring but may be transmitted to a second or a number of subsequent generations, through non-genomic mechanisms. While the transmission of ‘programmed’ effects through the maternal line could occur as a consequence of multiple influences, for example, altered maternal physiology, the inheritance of effects through the male line is more difficult to explain and there is much interest in a potential role for transgenerational epigenetic inheritance. In this review, we will discuss the mechanisms by which induced effects may be transmitted through the paternal lineage, with a particular focus on the role of epigenetic inheritance.
This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Metabolic programming in early life in humans
Authors: Fall Caroline H. D. , Kumaran Kalyanaraman 
Published: February 2019

An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic disease. High birth weight caused by maternal gestational diabetes is also associated with later diabetes, suggesting that fetal over-nutrition also has programming effects. Post-natal factors (excess weight gain/obesity, smoking, poor diets and physical inactivity) interact with fetal exposures to increase disease risk. Animal studies have shown permanent metabolic effects in offspring after alterations to maternal or early post-natal diets but evidence in humans is largely limited to observational and quasi-experimental situations such as maternal famine exposure. Randomized trials of maternal nutritional interventions during pregnancy have so far had limited follow-up of the offspring. Moreover, interventions usually started after the first trimester and therefore missed key peri-conceptional or early pregnancy events such as epigenetic changes, placentation and fetal organogenesis. Recent and ongoing trials intervening pre-conceptionally and powered for long-term offspring follow-up will address these issues. While current preventive strategies for cardio-metabolic disease focus on high-risk individuals in mid-life, DOHaD concepts offer a ‘primordial’ preventive strategy to reduce disease in future generations by improving fetal and infant development.
This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Cross-cultural evidence does not support universal acceleration of puberty in father-absent households
Authors: Sear Rebecca , Sheppard Paula , Coall David A. 
Published: February 2019

Father absence in early life has been shown to be associated with accelerated reproductive development in girls. Evolutionary social scientists have proposed several adaptive hypotheses for this finding. Though there is variation in the detail of these hypotheses, they all assume that family environment in early life influences the development of life-history strategy, and, broadly, that early reproductive development is an adaptive response to father absence. Empirical evidence to support these hypotheses, however, has been derived from WEIRD (Western, Educated, Industrialized, Rich and Democratic) populations. Data from a much broader range of human societies are necessary in order to properly test adaptive hypotheses. Here, we review the empirical literature on father absence and puberty in both sexes, focusing on recent studies that have tested this association beyond the WEIRD world. We find that relationships between father absence and age at puberty are more varied in contexts beyond WEIRD societies, and when relationships beyond the father–daughter dyad are considered. This has implications for our understanding of how early-life environment is linked to life-history strategies, and for our understanding of pathways to adult health outcomes, given that early reproductive development may be linked to negative health outcomes in later life
This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Clinical, imaging genetics and deformation based morphometry study of longitudinal changes after surgery for intractable aggressive behaviour
Authors: Gouveia Flavia V. , Germann Jürgen , de Morais Rosa M. C. B. , Fonoff Erich T. , Hamani Clement , Alho Eduardo Joaquim , Brentani Helena , Martins Ana Paula , Devenyi Gabriel , Patel Raihaan , Steele Christopher J. , Gramer Robert , Chakravarty M. Mallar , Martinez Raquel C. R. 
Published: February 2019

ABSTRACTIntractable aggressive behaviour is a devastating behavioural disorder that reach 30% of psychiatric aggressive patients. Neuromodulatory surgeries may be treatment alternatives to reduce suffering. We investigated the outcomes of bilateral amygdala radiofrequency ablation in four patients with intractable aggressive behaviour (life-threatening-self-injury and social aggression) by studying whole brain magnetic resonance imaging and clinical data. Post-surgery assessments revealed decreases in aggression and agitation and improvements in quality of life. Aggressive behaviour was positively correlated with serum testosterone levels and the testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses revealed preoperative amygdala volumes within normal range and confirmed appropriate lesion locations. Reduction in aggressiveness were accompanied by volumetric reduction in brain areas associated with aggressive behaviour (express genes related to aggressive behaviour), and increases in regions related to somatosensation. These findings further elucidates the neurocircuitry of aggression and suggests novel neuromodulation targets.
Does insulin signalling decide glucose levels in the fasting steady state?
Authors: Diwekar-Joshi Manawa , Watve Milind 
Published: February 2019

AbstractRecent work has suggested that altered insulin signalling may not be central and as critical to the pathophysiology of type 2 diabetes as classically believed. We critically re-examine the role of insulin in glucose homeostasis using five different approaches namely (i) systematic review and meta-analysis of tissue specific insulin receptor knock-out experiments in rodents, (ii) systematic review and meta-analysis of insulin suppression and insulin enhancement experiments in rodents and humans, (iii) differentiating steady-state and post-meal state glucose levels in streptozotocin treated rats in primary experiments (iv) mathematical and theoretical considerations and (v) glucose insulin relationship in human epidemiological data. All the approaches converge on the inference that although insulin action is needed to reach a homeostatic steady-state of glucose in fasting condition, there is no evidence that insulin action determines the steady-state level of glucose. A wider scale implication of the analysis is in emphasizing the need to differentiate steady state causality from perturbed state causality or on a broader scale driver causality from navigator causality in biology. A driver cause is a factor which is necessary to attain a destination but does not by itself decide the destination. A navigator cause, on the other hand, is one which by itself may not be sufficient to drive the system to a destination but which plays a role in deciding the destination or direction. Insulin appears to be a driver but not a navigator for glucose homeostasis. All evidence suggests that insulin action is required for reaching a homeostatic steady state, but it does not determine the steady-state level of glucose.
Central and peripheral innervation patterns of defined axial motor units in larval zebrafish
Authors: Bello-Rojas Saul , Istrate Ana E. , Kishore Sandeep , McLean David L. 
Published: February 2019

AbstractSpinal motor neurons and the peripheral muscle fibers they innervate form discrete motor units that execute movements of varying force and speed. Subsets of spinal motor neurons also exhibit axon collaterals that influence motor output centrally. Here, we have usedin vivoimaging to anatomically characterize the central and peripheral innervation patterns of axial motor units in larval zebrafish. Using early born ‘primary’ motor neurons and their division of epaxial and hypaxial muscle into four distinct quadrants as a reference, we define three distinct types of later born ‘secondary’ motor units. The largest are ‘m-type’ units, which innervate deeper fast-twitch muscle fibers via medial nerves. Next in size are ‘ms-type’ secondaries, which innervate superficial fast-twitch and slow fibers via medial and septal nerves, followed by ‘s-type’ units, which exclusively innervate superficial slow muscle fibers via septal nerves. All types of secondaries innervate up to four axial quadrants. Central axon collaterals are found in subsets of primaries based on soma position and predominantly in secondary fast-twitch units (m, ms) with increasing likelihood based on number of quadrants innervated. Collaterals are labeled by synaptophysin-tagged fluorescent proteins, but not PSD95, consistent with their output function. Also, PSD95 dendrite labeling reveals that larger motor units receive more excitatory synaptic input. Collaterals are largely restricted to the neuropil, however perisomatic connections are observed between motor units. These observations suggest that recurrent interactions are dominated by motor neurons recruited during stronger movements and set the stage for functional investigations of recurrent motor circuitry in larval zebrafish.
Drivers of individual oak tree selection by acorn dispersing animals inferred from a genotyped seedling cohort
Authors: Gerzabek Gabriel , Klein Etienne K. , Hampe Arndt 
Published: February 2019

ABSTRACTSeed-dispersing animals can strongly influence plant reproductive success and resulting population structures. Few studies have disentangled different drivers of disperser foraging behavior in natural settings and their actual relevance for plant fitness. Here we adopt a novel approach to investigate the drivers of individual trees’ dispersal success in a mixed Pedunculate oak-Pyrenean oak (Quercus robur and Q. pyrenaica) forest stand. We genotyped a seedling cohort (n = 825) upon emergence and performed Bayesian parentage analyses to infer the acorn dispersal success of each oak tree in the stand. We then modeled this estimate as a function of six tree characteristics. The absolute number of animal-dispersed seedlings was exclusively predicted by crop size and the proportion of dispersed seedlings by the number of fruiting oaks in the neighborhood. Neither the oak species nor tree height, acorn size or shape played any role. Our findings contrast with results from experimental studies and suggest that effective acorn dispersers, despite being scatter-hoarders, behaved much like avian dispersers of fleshy-fruited species when selecting trees to forage on. Their behavior should favor the dominance of large, prolific trees for the dynamics and genetic composition of naturally regenerating oak stands.
Generation of dual specific bivalent BiTEs (dbBIspecific T-cell Engaging antibodies) for cellular immunotherapy
Authors: Kujawski Maciej , Li Lin , Bhattacharya Supriyo , Wong Patty , Lee Wen-Hui , Williams Lindsay , Li Harry , Chea Junie , Poku Kofi , Bowles Nicole , Vaidehi Nagarajan , Yazaki Paul , Shively John E. 
Published: February 2019

AbstractBispecific T-cell engaging antibodies (BiTES), comprising dual anti-CD3 and anti-tumor antigen scFv fragments, are important therapeutic agents for the treatment of cancer. The dual scFv construct for BiTES requires proper protein folding while their small molecular size leads to rapid kidney clearance. Here we show that an intact (150 kDa) anti-tumor antigen antibody to CEA was joined in high yield (ca. 30%) to intact (150 kDa) anti-murine and anti-human CD3 antibodies using hinge region specific Click chemistry to form dual-specific, bivalent BiTES (db BiTES, 300 kDa). The interlocked hinge regions are compatible with a structural model that fits the electron micrographs of the 300 kDa particles. Compared to intact anti-CEA antibody, dbBiTES maintain high in vivo tumor targeting as demonstrated by PET imaging, and redirect dbBiTE coated T-cells (1 microgram/10 million cells) to kill CEA+ target cells both in vitro, and in vivo in CEA transgenic mice.
Personalized Therapy Design for Systemic Lupus Erythematosus Based on the Analysis of Protein-Protein Interaction Networks
Authors: Brant Elizabeth J. , Rietman Edward A. , Klement Giannoula Lakka , Cavaglia Marco , Tuszynski Jack A. 
Published: February 2019

AbstractWe analyzed protein expression data for Lupus patients, which have been obtained from publicly available databases. A combination of systems biology and statistical thermodynamics approaches was used to extract topological properties of the associated protein-protein interaction networks for each of the 291 patients whose samples were used to provide the molecular data. We have concluded that among the many proteins that appear to play critical roles in this pathology, most of them are either ribosomal proteins, ubiquitination pathway proteins or heat shock proteins. We propose some of the proteins identified in this study to be considered for drug targeting.
A direct link betweenPrss53, hair curvature, and skeletal dysplasia
Authors: Deng Jichao , Song Yuning , Liu Hongmei , Sui Tingting , Chen Mao , Zhang Yuxin , Yao Bing , Xu Yuxin , Liu Zhiquan , Lai Liangxue , Li Zhanjun 
Published: February 2019

AbstractIn humans, protease serine S1 family member 53 (Prss53) is highly expressed in the hair follicle, especially the inner root sheath, which is associated with hair shape according to recent genome-wide association study (GWAS) data. However, no animal evidence has indicated a link betweenPrss53and hair shape to date. Here, we used CRISPR/Cas9 to generatePrss53-mutated rabbits. The homozygous (Prss53-/-) rabbits exhibited curved hair and skeletal dyskinesia with severe malformation, while the heterozygous (Prss53+/-) rabbits did not exhibit these features. The curvature features of the hair were accompanied by lesions that were generally denser and less well-defined in the cuticular septation of the hair shaft, and the compartments of the hair follicle were incomplete, as evidenced by decreased expression levels of keratinocyte differentiation genes. In addition, skeletal dysplasia, an increased lethality rate and decreased plasma calcium and serum alkaline phosphatase (ALP) levels were determined in thePrss53-/-rabbits. Furthermore, disrupted calcium metabolism, which may play a role in the hair curvature and skeletal dysplasia ofPrss53+/-rabbits, was demonstrated by using high-throughput RNA sequencing data. Thus, our study confirmed for the first time that the loss ofPrss53lead to curved hair in animals and provides new insights into the crucial role ofPrss53in calcium metabolism.Author SummaryNo animal evidence has indicated a link betweenPrss53and hair shape to date.ThePrss53-/-rabbits exhibited curved hair and skeletal dyskinesia.The disrupted calcium metabolism may play a role in the hair curvature and skeletal dysplasia ofPrss53+/-rabbits.