bluuebunny/crossref_metadata_2025 huggingface dataset:
New layer-structured ferroelectric polycrystalline materials, Na0.5NdxBi4.5−xTi4O15: crystal structures, electrical properties and conduction behaviors
Authors: Long Changbai , Chang Qi , Wu Yun , He Weifeng , Li Yinghong , Fan Huiqing
Published: July 2015

Structure refinement for Aurivillius ferroelectric Na0.5Nd0.5Bi4Ti4O15and evolutions inTc,PrandEcwith the increasingxvalue in Na0.5NdxBi4.5−xTi4O15.
ATP stimulates pannexin 1 internalization to endosomal compartments
Authors: Boyce Andrew K.J. , Kim Michelle S. , Wicki-Stordeur Leigh E. , Swayne Leigh Anne
Published: July 2015

The ubiquitous pannexin 1 (Panx1) ion- and metabolite-permeable channel mediates the release of ATP, a potent signalling molecule. In the present study, we provide striking evidence that ATP, in turn, stimulates internalization of Panx1 to intracellular membranes. These findings hold important implications for understanding the regulation of Panx1 when extracellular ATP is elevated. In the nervous system, this includes phenomena such as synaptic plasticity, pain, precursor cell development and stroke; outside of the nervous system, this includes things like skeletal and smooth muscle activity and inflammation. Within 15 min, ATP led to significant Panx1–EGFP internalization. In a series of experiments, we determined that hydrolysable ATP is the most potent stimulator of Panx1 internalization. We identified two possible mechanisms for Panx1 internalization, including activation of ionotropic purinergic (P2X) receptors and involvement of a putative ATP-sensitive residue in the first extracellular loop of Panx1 (Trp74). Internalization was cholesterol-dependent, but clathrin, caveolin and dynamin independent. Detailed analysis of Panx1 at specific endosome sub-compartments confirmed that Panx1 is expressed in endosome membranes of the classical degradation pathway under basal conditions and that elevation of ATP levels diverts a sub-population to recycling endosomes. This is the first report detailing endosome localization of Panx1 under basal conditions and the potential for ATP regulation of its surface expression. Given the ubiquitous expression profile of Panx1 and the importance of ATP signalling, these findings are of critical importance for understanding the role of Panx1 in health and disease.
Fully pipelined CORDIC‐based inverse kinematic FPGA design for biped robots
Authors: Chung Rih‐Lung , Zhang Yi‐Qin , Chen Shih‐Lun
Published: July 2015

A high‐speed field‐programmable gate array (FPGA) design is proposed to calculate angles and distances for biped robots in real time. A low‐complexity and high‐accuracy hardware‐oriented algorithm based on CORDIC was developed. To reduce hardware cost, a hardware sharing technique was used to realise a CORDIC scaling factor generator and three hardware sharing machines. Moreover, the multipliers and dividers were replaced by cost‐efficiency components, such as adders and shifters to further reduce hardware cost. In addition, the proposed design was implemented with a fully pipelined architecture, which achieved improved operating frequency and throughput efficiency. The proposed design was realised and verified by an FPGA device with a maximum operating frequency of 127 MHz, which achieved the calculation of angles and distances for biped robots in real time. Compared with the previous design, this work not only reduced hardware cost by at least 49.6% and average errors by at least 67.2%, but also improved the average executing performance by 62.7% when calculating ten angles for the biped robots.
Measurement of reflectivity of spherically bent crystals using Kα signal from hot electrons produced by laser-matter interaction
Authors: Antonelli L. , Forestier-Colleoni P. , Folpini G. , Bouillaud R. , Faenov A. , Fedeli L. , Fourment C. , Giuffrida L. , Hulin S. , Pikuz S. , Santos J. J. , Volpe L. , Batani D.
Published: July 2015

In an experiment at the laser facility ECLIPSE of the CELIA laboratory, University of Bordeaux, we measure the reflectivity of spherically bent crystals that are commonly used to investigate the propagation of fast electrons through the Kα radiation they generate in matter. The experimental reflectivity compares well with predictions from a ray-tracing code that takes into account the specific geometry, although the crystals seem to suffer from aging problems.
Origin of structural analogies and differences between the atomic structures of GeSe4 and GeS4 glasses: A first principles study
Authors: Bouzid Assil , Le Roux Sébastien , Ori Guido , Boero Mauro , Massobrio Carlo
Published: July 2015

First-principles molecular dynamics simulations based on density functional theory are employed for a comparative study of structural and bonding properties of two stoichiometrically identical chalcogenide glasses, GeSe4 and GeS4. Two periodic cells of 120 and 480 atoms are adopted. Both glasses feature a coexistence of Ge-centered tetrahedra and Se(S) homopolar connections. Results obtained for N = 480 indicate substantial differences at the level of the Se(S) environment, since Ge–Se–Se connections are more frequent than the corresponding Ge–S–S ones. The presence of a more prominent first sharp diffraction peak in the total neutron structure factor of glassy GeS4 is rationalized in terms of a higher number of large size rings, accounting for extended Ge–Se correlations. Both the electronic density of states and appropriate electronic localization tools provide evidence of a higher ionic character of Ge–S bonds when compared to Ge–Se bonds. An interesting byproduct of these investigations is the occurrence of discernible size effects that affect structural motifs involving next nearest neighbor distances, when 120 or 480 atoms are used.
Close contact with spontaneously cycling Saint Croix ewes triggers cyclic activity in seasonally anestrous Suffolk ewes
Authors: Orihuela Agustín , Clemente Neftalí , Ungerfeld Rodolfo
Published: July 2015

In domestic goats, oestrous activity may be induced by close contact with cyclic females. As tropical breeds of sheep show light seasonality or are even unaffected by season, the purpose of this study was to examine the hypothesis that cyclic activity may be induced in anestrous Suffolk ewes by close contact with spontaneously cycling Saint Croix ewes. The experiment was conducted with 17 anestrous Suffolk ewes that were assigned to one of two groups. Although Suffolk ewes in the Control group (n = 9) remained isolated, those of the treated group (n = 8) were joined (Day 0) and maintained in close contact with 20 Saint Croix ewes for 38 days. Serum progesterone concentration was measured in all ewes in blood samples collected on Days –8, –2, 8, 13, 18, 23, 28, 33 and 38. Before Day 0, 17/20 Saint Croix ewes were cycling, but no Suffolk ewe had luteal levels of progesterone. By Day 13, more treated than Control Suffolk ewes had progesterone luteal concentrations (8/8 vs 1/9; P = 0.0004). It was concluded that spontaneously cycling Saint Croix ewes induce cyclic activity in anestrous Suffolk ewes.
The effect of the concentration and feeding duration of spray-dried plasma protein on growth performance, digestive enzyme activities, nutrient digestibility and intestinal mucosal development of broiler chickens
Authors: Beski S. S. M. , Swick R. A. , Iji P. A.
Published: July 2015

This study was undertaken to investigate the effect of the supplementation level and feeding duration of spray-dried porcine plasma (SDPP) on performance and digestive physiology of broiler chickens. Three inclusion levels of SDPP (0, 10 or 20 g/kg) were used in lieu of meat meal and fed from hatch to 5 or 10 days of age. At Day 10, there was an interaction (P < 0.05) between the inclusion level and feeding duration of SDPP, improving bodyweight (BW) in birds that received SDPP at the highest concentration over the longer feeding duration. Inclusion of SDPP resulted in lower (P < 0.01) feed intake, higher (P < 0.01) BW and improved (P < 0.05) feed conversion ratio (FCR). Furthermore, FCR was improved (P < 0.001) in birds that were offered SDPP over the longer feeding duration than in those that received SDPP for a shorter duration. The pancreas was heavier (P < 0.05) in the birds that received SDPP at the highest concentration over the long feeding duration. At 24 days of age, there was an interaction (P < 0.05) between the inclusion level and feeding duration of SDPP, indicating the lowest amino acid, protein, gross energy and dry matter digestibility in the birds that received SDPP at the highest concentration over the longer feeding duration. Villus height was increased (P < 0.001) by the experimental factors and their interaction, revealing longer villi in the birds that received SDPP at the low level over the short feeding duration. Apparent villus surface area was higher (P < 0.001) in birds that were offered diets that contained the highest concentration of SDPP. There was an interaction (P < 0.01) between experimental factors with regards to the apparent villus surface area. Up to Day 35, the level of SDPP tended to increase (P = 0.06) BW. Level (P < 0.001) and feeding duration (P < 0.01) improved FCR in the birds that received SDPP for the long feeding duration. It would be more economical to use a low inclusion level of SDPP over a longer period of time to achieve the same benefits.
Microplastic contamination in an urban area: a case study in Greater Paris
Authors: Dris Rachid , Gasperi Johnny , Rocher Vincent , Saad Mohamed , Renault Nicolas , Tassin Bruno
Published: July 2015

Environmental context
Plastics production has increased considerably in recent years, leading to pollution by plastics, including microplastics (comprising particles smaller than 5mm). This work addresses the issue of microplastics from urban sources and in receiving waters in Greater Paris. Microplastics were found in all urban compartments investigated, namely atmospheric fallout, waste- and treated water, and surface water.

Abstract
This study investigates the microplastic contamination of both urban compartments (wastewater and total atmospheric fallout) and surface water in a continental environment. These first investigations on an urban environment confirm the presence of microplastics in sewage, fresh water and total atmospheric fallout and provide knowledge on the type and size distribution of microplastics in the 100–5000-µm range. For the first time, the presence of microplastics, mostly fibres, is highlighted in total atmospheric fallout (29–280particlesm–2day–1). High levels of fibres were found in wastewater (260–320×103particlesm–3). In treated effluent, the contamination significantly decreased to 14–50×103particlesm–3. In the River Seine, two sampling devices were used to collect both large and small microplastic particles: (i) a plankton net (80-µm mesh), and (ii) a manta trawl (330-µm mesh). Sampling with the plankton net showed a predominance of fibres, with concentrations ranging from 3 to 108particlesm–3. A greater diversity of both microplastic shapes and types was found during manta trawl sampling but at much lower concentrations (0.28–0.47particlesm–3). This combined approach could be relevant and implemented in future studies to provide an accurate overview of microplastic distribution in freshwater.
Aspects of the reproductive biology of dusky, spinner and sandbar sharks (Family Carcharhinidae) from the Tasman Sea
Authors: Geraghty Pascal T. , Macbeth William G. , Williamson Jane E.
Published: July 2015

Increased harvest pressure exerted on sharks worldwide has created a necessity for more information concerning the basic biology of targeted species. This study marks the first dedicated assessment of the reproductive biology of Carcharhinus obscurus, C. brevipinna and C. plumbeus in eastern Australian waters, where these species support a demersal longline fishery. We found all three to be late maturing species of low reproductive output, suggestive of an overarching susceptibility to stock depletion in the region. Length- (L50, cm LT) and age-at-maturity (A50, years), for females and males were respectively 281.1 and 15.5, and 271.9 and 14.6 for C. obscurus; 224.9 and 10.1, and 208.9 and 8.5 for C. brevipinna; and, 174.8 and 9.5, and 164.5 and 7.0 for C. plumbeus. Uterine fecundity (i.e. litter size) was observed at 5–12 (=9.6), 5–14 (=10.6) and 3–12 (=7.8) for the same three species respectively, and increased significantly with maternal length in C. brevipinna. Length-at-birth (L0, cm LT) ranged from 92 to 96 for C. obscurus, 79–82 for C. brevipinna and 66–76 for C. plumbeus, and all three species exhibited lengthy gestation periods, overall embryonic sex ratios of 1:1 and synchronous parturition in autumn. However, given limitations with respect to sample size and temporal distribution inherent in this study, the reproductive parameters defined herein are necessarily preliminary. Nevertheless, this research challenges a range of findings emanating from other parts of the world and, in doing so, raises pertinent questions relating to the resilience to targeted fishing activities of these species in New South Wales waters compared to other oceanic regions. Moreover, it reinforces the importance of locally derived demographic parameters for population modelling and stock assessment.
Wandering wetlands: spatial patterns of historical channel and floodplain change in the Ramsar-listed Macquarie Marshes, Australia
Authors: Ralph Timothy J. , Hesse Paul P. , Kobayashi Tsuyoshi
Published: July 2015

In the context of static conservation reserves, dynamic fluvial processes and patterns of river channel and floodplain change are problematic for environmental management. Floodplain wetlands that evolve by erosion and sedimentation experience changes in the location and extent of channels and wetlands regardless of conservation reserve boundaries. We describe historical channel and floodplain change in an Australian wetland of international ecological significance, the southern Macquarie Marshes, and synthesise the role of avulsion in wetlands that move laterally on the broader floodplain. Avulsion has shifted the foci of flooding and areas of aquatic habitat in the system over the last century. By ~1925, active wetlands surrounding the Old Macquarie River and the original conservation area contracted around Monkeygar Creek within the present nature reserve, and the boundary of this reserve has changed little since the 1940s. Ecological changes associated with continued wetland desiccation in the reserve triggered a recent Ramsar Article 3.2 notification for the Macquarie Marshes, prompting management responses from government agencies. Fluvial morphodynamics and their impacts on wetland ecology should be specifically recognised and integrated with adaptive management plans to combine new findings with lessons learned from previous intervention strategies for the long-term ecological sustainability of floodplain wetlands.
Typhoon effects on phytoplankton responses in a semi-closed freshwater ecosystem
Authors: Ko Chia-Ying , Lai Chao-Chen , Chen Tzong-Yueh , Hsu Huang-Hsiung , Shiah Fuh-Kwo
Published: July 2015

Analyses of past typhoons have suggested that global climate change may result in increases in the intensity of these episodic events and that the effects of typhoons on the biogeochemistry of aquatic ecosystems will also be strengthened. We collected a 2-year time series of phytoplankton responses, including chlorophyll-a concentration, primary production and turnover rate in the Fei-Tsui Reservoir, Taiwan, on the basis of five typhoons in 2011 and eight in 2012 (21 weeks affected). We found approximately a two-fold increase in phytoplankton responses during the typhoon period compared with the non-typhoon period. However, there were no consistent correlations between phytoplankton responses and typhoon disturbance and length of typhoon stay. Vertical distributions of phytoplankton responses indicated that the peak values of these responses occurred both during the typhoon periods and during the non-typhoon periods occurring between two typhoons. Moreover, the strongest correlations were found between euphotic depth-averaged phosphate and primary production and turnover rate. Combined effects on phytoplankton responses could explain at least 70% of the variability. The regulation of phytoplankton responses by multiple processes and interactions among factors that operate during each typhoon event may add complexity to the challenge of detecting typhoon-driven mechanisms in such ecosystems.
Assessment of yellowtail kingfish (Seriola lalandi) as a surrogate host for the production of southern bluefin tuna (Thunnus maccoyii) seed via spermatogonial germ cell transplantation
Authors: Bar Ido , Smith Andre , Bubner Erin , Yoshizaki Goro , Takeuchi Yutaka , Yazawa Ryosuke , Chen Ben Nan , Cummins Scott , Elizur Abigail
Published: July 2015

Germ cell transplantation is an innovative technology for the production of interspecies surrogates, capable of facilitating easier and more economical management of large-bodied broodstock, such as the bluefin tuna. The present study explored the suitability of yellowtail kingfish (Seriola lalandi) as a surrogate host for transplanted southern bluefin tuna (Thunnus maccoyii) spermatogonial cells to produce tuna donor-derived gametes upon sexual maturity. Germ cell populations in testes of donor T. maccoyii males were described using basic histology and the molecular markers vasa and dead-end genes. The peripheral area of the testis was found to contain the highest proportions of dead-end-expressing transplantable Type A spermatogonia. T. maccoyii Type A spermatogonia-enriched preparations were transplanted into the coelomic cavity of 6–10-day-old post-hatch S. lalandi larvae. Fluorescence microscopy and polymerase chain reaction analysis detected the presence of tuna cells in the gonads of the transplanted kingfish fingerlings at 18, 28, 39 and 75 days after transplantation, indicating that the transplanted cells migrated to the genital ridge and had colonised the developing gonad. T. maccoyii germ cell-derived DNA or RNA was not detected at later stages, suggesting that the donor cells were not maintained in the hosts’ gonads.
Keap1 regulates inflammatory signaling in
Mycobacterium avium
-infected human macrophages
Authors: Awuh Jane Atesoh , Haug Markus , Mildenberger Jennifer , Marstad Anne , Do Chau Phuc Ngoc , Louet Claire , Stenvik Jørgen , Steigedal Magnus , Damås Jan Kristian , Halaas Øyvind , Flo Trude Helen
Published: July 2015

Significance

Inflammatory signaling is a central mechanism controlling host defenses to pathogens. Members of
Mycobacterium avium
complex cause disease in immunocompromised patients and in individuals with predisposing lung abnormalities. We provide evidence of a mechanism in human primary macrophages whereby the oxidative stress sensor Kelch-like ECH-associated protein 1 (Keap1) negatively regulates inflammatory responses and thus facilitates intracellular growth of
M. avium
. Our findings are of high biological and clinical significance, as opportunistic infections with nontuberculous mycobacteria are receiving renewed attention because of increased incidence and difficulties in treatment. Altered Keap1 gene expression may also have vital clinical implications for other inflammation-associated conditions, opening novel research venues for translational research, for instance in the expanding field of host-targeted therapy for infectious diseases.
Study of the instability of the Poiseuille flow using a thermodynamic formalism
Authors: Wang Jianchun , Li Qianxiao , E Weinan
Published: July 2015

Significance

The stability of Poiseuille flow is among the most classical problems in fluid mechanics going back to the pioneering work of Reynolds. Despite a huge amount of effort, particularly recent advances in experimental studies, we still lack a suitable theoretical framework. In this paper, we develop a thermodynamic formalism for studying this problem. We show that this formalism allows us to identify a unique critical Reynolds number at which the laminar flow loses stability. We also study the free energy, action, and other thermodynamic relations for the macroscopic quantities associated with the flow. The formalism developed here should be applicable to a large class of problems exhibiting subcritical instabilities.
Toward an evolutionary model of cancer: Considering the mechanisms that govern the fate of somatic mutations
Authors: Rozhok Andrii I. , DeGregori James
Published: July 2015

Our understanding of cancer has greatly advanced since Nordling [Nordling CO (1953)
Br J Cancer
7(1):68–72] and Armitage and Doll [Armitage P, Doll R (1954)
Br J Cancer
8(1):1–12] put forth the multistage model of carcinogenesis. However, a number of observations remain poorly understood from the standpoint of this paradigm in its contemporary state. These observations include the similar age-dependent exponential rise in incidence of cancers originating from stem/progenitor pools differing drastically in size, age-dependent cell division profiles, and compartmentalization. This common incidence pattern is characteristic of cancers requiring different numbers of oncogenic mutations, and it scales to very divergent life spans of mammalian species. Also, bigger mammals with larger underlying stem cell pools are not proportionally more prone to cancer, an observation known as Peto’s paradox. Here, we present a number of factors beyond the occurrence of oncogenic mutations that are unaccounted for in the current model of cancer development but should have significant impacts on cancer incidence. Furthermore, we propose a revision of the current understanding for how oncogenic and other functional somatic mutations affect cellular fitness. We present evidence, substantiated by evolutionary theory, demonstrating that fitness is a dynamic environment-dependent property of a phenotype and that oncogenic mutations should have vastly different fitness effects on somatic cells dependent on the tissue microenvironment in an age-dependent manner. Combined, this evidence provides a firm basis for understanding the age-dependent incidence of cancers as driven by age-altered systemic processes regulated above the cell level.
Consequences of clonality for sexual fitness: Clonal expansion enhances fitness under spatially restricted dispersal
Authors: Van Drunen Wendy E. , van Kleunen Mark , Dorken Marcel E.
Published: July 2015

Clonality is a pervasive feature of sessile organisms, but this form of asexual reproduction is thought to interfere with sexual fitness via the movement of gametes among the modules that comprise the clone. This within-clone movement of gametes is expected to reduce sexual fitness via mate limitation of male reproductive success and, in some cases, via the production of highly inbred (i.e., self-fertilized) offspring. However, clonality also results in the spatial expansion of the genetic individual (i.e., genet), and this should decrease distances gametes and sexually produced offspring must travel to avoid competing with other gametes and offspring from the same clone. The extent to which any negative effects of clonality on mating success might be offset by the positive effects of spatial expansion is poorly understood. Here, we develop spatially explicit models in which fitness was determined by the success of genets through their male and female sex functions. Our results indicate that clonality serves to increase sexual fitness when it is associated with the outward expansion of the genet. Our models further reveal that the main fitness benefit of clonal expansion might occur through the dispersal of offspring over a wider area compared with nonclonal phenotypes. We conclude that, instead of interfering with sexual reproduction, clonal expansion should often serve to enhance sexual fitness.
Impermanence of bacterial clones
Authors: Bobay Louis-Marie , Traverse Charles C. , Ochman Howard
Published: July 2015

Bacteria reproduce asexually and pass on a single genome copied from the parent, a reproductive mode that assures the clonal descent of progeny; however, a truly clonal bacterial species is extremely rare. The signal of clonality can be interrupted by gene uptake and exchange, initiating homologous recombination that results in the unique sequence of one clone being incorporated into another. Because recombination occurs sporadically and on local scales, these events are often difficult to recognize, even when considering large samples of completely sequenced genomes. Moreover, several processes can produce the appearance of clonality in populations that undergo frequent recombination. The rates and consequences of recombination have been studied in
Escherichia coli
for over 40 y, and, during this time, there have been several shifting views of its clonal status, population structure, and rates of gene exchange. We reexamine the studies and retrace the evolution of the methods that have assessed the extent of DNA flux, largely focusing on its impact on the
E. coli
genome.
Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life
Authors: Speijer Dave , Lukeš Julius , Eliáš Marek
Published: July 2015

Sexual reproduction and clonality in eukaryotes are mostly seen as exclusive, the latter being rather exceptional. This view might be biased by focusing almost exclusively on metazoans. We analyze and discuss reproduction in the context of extant eukaryotic diversity, paying special attention to protists. We present results of phylogenetically extended searches for homologs of two proteins functioning in cell and nuclear fusion, respectively (HAP2 and GEX1), providing indirect evidence for these processes in several eukaryotic lineages where sex has not been observed yet. We argue that (
i
) the debate on the relative significance of sex and clonality in eukaryotes is confounded by not appropriately distinguishing multicellular and unicellular organisms; (
ii
) eukaryotic sex is extremely widespread and already present in the last eukaryotic common ancestor; and (
iii
) the general mode of existence of eukaryotes is best described by clonally propagating cell lines with episodic sex triggered by external or internal clues. However, important questions concern the relative longevity of true clonal species (i.e., species not able to return to sexual procreation anymore). Long-lived clonal species seem strikingly rare. We analyze their properties in the light of meiotic sex development from existing prokaryotic repair mechanisms. Based on these considerations, we speculate that eukaryotic sex likely developed as a cellular survival strategy, possibly in the context of internal reactive oxygen species stress generated by a (proto) mitochondrion. Thus, in the context of the symbiogenic model of eukaryotic origin, sex might directly result from the very evolutionary mode by which eukaryotic cells arose.
Does the avoidance of sexual costs increase fitness in asexual invaders?
Authors: Stelzer Claus-Peter
Published: July 2015

The high prevalence of sexual reproduction is considered a paradox mainly for two reasons. First, asexuals should enjoy various growth benefits because they seemingly rid themselves of the many inefficiencies of sexual reproduction—the so-called costs of sex. Second, there seems to be no lack of asexual origins because losses of sexual reproduction have been described in almost every larger eukaryotic taxon. Current attempts to resolve this paradox concentrate on a few hypotheses that provide universal benefits that would compensate for these costs and give sexual reproduction a net advantage. However, are new asexual lineages really those powerful invaders that could quickly displace their sexual ancestors? Research on the costs of sex indicates that sex is often stabilized by highly lineage-specific mechanisms. Two main categories can be distinguished. First are beneficial traits that evolved within a particular species and became tightly associated with sex (e.g., a mating system that involves sexual selection, or a sexual diapausing stage that allows survival through harsh periods). If such traits are absent in asexuals, simple growth efficiency considerations will not capture the fitness benefits gained by skipping sexual reproduction. Second, lineage-specific factors might prevent asexuals from reaching their full potential (e.g., dependence on fertilization in sperm-dependent parthenogens). Such observations suggest that the costs of sex are highly variable and often lower than theoretical considerations suggest. This has implications for the magnitude of universal benefits required to resolve the paradox of sex.
Preventing clonal evolutionary processes in cancer: Insights from mathematical models
Authors: Rodriguez-Brenes Ignacio A. , Wodarz Dominik
Published: July 2015

Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze treatment responses, and aid in the design of treatment strategies to combat the emergence of drug-resistant cells. The discussion will be done in the context of specific examples. Among defense mechanisms, we explore how replicative limits and cellular senescence induced by telomere shortening can influence the emergence and evolution of tumors. Among treatment approaches, we consider the targeted treatment of chronic lymphocytic leukemia (CLL) with tyrosine kinase inhibitors. We illustrate how basic evolutionary mathematical models have the potential to make patient-specific predictions about disease and treatment outcome, and argue that evolutionary models could become important clinical tools in the field of personalized medicine.
Cloning humans? Biological, ethical, and social considerations
Authors: Ayala Francisco J.
Published: July 2015

There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits.
Cancer in the parasitic protozoans
Trypanosoma brucei
and
Toxoplasma gondii
Authors: Lun Zhao-Rong , Lai De-Hua , Wen Yan-Zi , Zheng Ling-Ling , Shen Ji-Long , Yang Ting-Bo , Zhou Wen-Liang , Qu Liang-Hu , Hide Geoff , Ayala Francisco J.
Published: July 2015

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as
Trypanosoma brucei,
a blood parasite, and
Toxoplasma gondii,
an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.
Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output
Authors: Wefelmeyer Winnie , Cattaert Daniel , Burrone Juan
Published: July 2015

Significance

Neurons integrate synaptic inputs at the axon initial segment (AIS), where the action potential is initiated. Recent findings have shown this structure to be highly plastic. Here, we focus on the axo-axonic synapses formed onto the AIS and show that although chronic increases in neuronal activity result in a distal relocation of the AIS, the synapses do not change position. Computational modeling suggests this spatial mismatch has critical functional consequences on neuronal output, allowing the cell to downregulate its own excitability and thus respond homeostatically to chronic stimulation.
Clonal reproduction in fungi
Authors: Taylor John W. , Hann-Soden Christopher , Branco Sara , Sylvain Iman , Ellison Christopher E.
Published: July 2015

Research over the past two decades shows that both recombination and clonality are likely to contribute to the reproduction of all fungi. This view of fungi is different from the historical and still commonly held view that a large fraction of fungi are exclusively clonal and that some fungi have been exclusively clonal for hundreds of millions of years. Here, we first will consider how these two historical views have changed. Then we will examine the impact on fungal research of the concept of restrained recombination [Tibayrenc M, Ayala FJ (2012)
Proc Natl Acad Sci USA
109 (48):E3305–E3313]. Using animal and human pathogenic fungi, we examine extrinsic restraints on recombination associated with bottlenecks in genetic variation caused by geographic dispersal and extrinsic restraints caused by shifts in reproductive mode associated with either disease transmission or hybridization. Using species of the model yeast
Saccharomyces
and the model filamentous fungus
Neurospora
, we examine intrinsic restraints on recombination associated with mating systems that range from strictly clonal at one extreme to fully outbreeding at the other and those that lie between, including selfing and inbreeding. We also consider the effect of nomenclature on perception of reproductive mode and a means of comparing the relative impact of clonality and recombination on fungal populations. Last, we consider a recent hypothesis suggesting that fungi thought to have the most severe intrinsic constraints on recombination actually may have the fewest.
Earliest economic exploitation of chicken outside East Asia: Evidence from the Hellenistic Southern Levant
Authors: Perry-Gal Lee , Erlich Adi , Gilboa Ayelet , Bar-Oz Guy
Published: July 2015

Significance

This study offers new evidence on the cultural history of the chicken, a species that until recently received limited attention compared with other domesticated animals. We provide evidence for the earliest known economic exploitation of the chicken outside its original distribution. This intensified use is first documented in the Southern Levant during the Hellenistic period (fourth–second centuries B.C.E.), at least 100 y before chickens spread widely across Europe. We explore the mechanisms for the spread of chickens as an important species in livestock economies from Asian to Mediterranean and European economies in antiquity to become one of the most widespread and dominant domesticates in the world today.
Impact of fossil fuel emissions on atmospheric radiocarbon and various applications of radiocarbon over this century
Authors: Graven Heather D.
Published: July 2015

Significance

A wide array of scientific disciplines and industries use radiocarbon analyses; for example, it is used in dating of archaeological specimens and in forensic identification of human and wildlife tissues, including traded ivory. Over the next century, fossil fuel emissions will produce a large amount of CO2with no14C because fossil fuels have lost all14C over millions of years of radioactive decay. Atmospheric CO2, and therefore newly produced organic material, will appear as though it has “aged,” or lost14C by decay. By 2050, fresh organic material could have the same14C/C ratio as samples from 1050, and thus be indistinguishable by radiocarbon dating. Some current applications for14C may cease to be viable, and other applications will be strongly affected.
Regulation of ribosomal DNA amplification by the TOR pathway
Authors: Jack Carmen V. , Cruz Cristina , Hull Ryan M. , Keller Markus A. , Ralser Markus , Houseley Jonathan
Published: July 2015

Significance

We tend to think of our genome as an unchanging store of information; however, recent evidence suggests that genomes vary between different cells in the same organism. How these differences arise and what effects they have remain unknown, but clearly our genome can change. In a single-celled organism, genome changes occur at random, and advantageous changes slowly propagate by natural selection. However, it is known that the DNA encoding ribosomes can change simultaneously in a whole population. Here we show that signaling pathways that sense environmental nutrients control genome change at the ribosomal DNA. This demonstrates that not all genome changes occur at random and that cells possess specific mechanisms to optimize their genome in response to the environment.
Music training alters the course of adolescent auditory development
Authors: Tierney Adam T. , Krizman Jennifer , Kraus Nina
Published: July 2015

Significance

We show that in-school music training changes the course of adolescent brain development. Relative to an active control group that shows the expected wane in subcortical response consistency, adolescents undertaking in-school music training maintained heightened neural consistency throughout high school. The music training group also exhibited earlier emergence of the adult cortical response, suggesting that in-school music accelerates neurodevelopment. These changes seem to benefit literacy skills: both groups improved in phonological awareness relative to the general population, but the music training group improved more compared with the active controls. Our results support the notion that the adolescent brain remains receptive to training, underscoring the importance of enrichment during teenage years.
RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in
Caenorhabditis elegans
Authors: Seo Mihwa , Seo Keunhee , Hwang Wooseon , Koo Hee Jung , Hahm Jeong-Hoon , Yang Jae-Seong , Han Seong Kyu , Hwang Daehee , Kim Sanguk , Jang Sung Key , Lee Yoontae , Nam Hong Gil , Lee Seung-Jae V.
Published: July 2015

Significance

RNA helicases are a large family of enzymes that regulate the generation and maintenance of RNA. However, the physiologic roles of RNA helicases in animal aging remained unknown. Here we show that an RNA helicase, helicase 1 (HEL-1), extends the lifespan of the roundworm
Caenorhabditis elegans
by up-regulating the longevity transcription factor forkhead box O (FOXO). Our finding suggests that an RNA helicase can have rather specific roles in animal longevity. A number of studies show that variants of FOXO are linked to human aging and longevity. In addition, the mammalian HEL-1 homolog has been implicated in cellular aging. Thus, our work may have direct implications in mammalian aging, and the human HEL-1 homolog may work with FOXO to increase lifespan.
Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity
Authors: Weiskopf Daniela , Bangs Derek J. , Sidney John , Kolla Ravi V. , De Silva Aruna D. , de Silva Aravinda M. , Crotty Shane , Peters Bjoern , Sette Alessandro
Published: July 2015

Significance

Infections with any of the four dengue virus serotypes (DENV 1–4) are the most prevalent and rapidly spreading mosquito-borne viral infections in humans. There is no treatment or vaccine currently available. We found that the virus-specific cells display a highly polarized cytotoxic phenotype that correlated with expression of a protective HLA DR allele. Although the occurrence of cytotoxic CD4+T cells in humans has been described in the context of some chronic viral infections, to our knowledge, this is the first report of ex vivo cytotoxic CD4+activity after exposure with an acute virus. These results will help shed light on the specific role of CD4+T cells in DENV infection and may help in finding a correlate of protection.
How amide hydrogens exchange in native proteins
Authors: Persson Filip , Halle Bertil
Published: July 2015

Significance

Proteins tend to be compactly folded but occasionally undergo conformational fluctuations that expose even the most deeply buried parts of the polypeptide chain to external solvent. As a consequence, the backbone amide hydrogens can exchange with water hydrogens. Monitoring such hydrogen exchange is a well-established method for characterizing protein flexibility, even though the nature of the ‟open” exchange-competent state is unknown. We have used an ultralong computer simulation to identify the elusive open state as transient (100 ps), locally distorted conformations where the N–H group coordinates two water molecules.
Knockout silkworms reveal a dispensable role for juvenile hormones in holometabolous life cycle
Authors: Daimon Takaaki , Uchibori Miwa , Nakao Hajime , Sezutsu Hideki , Shinoda Tetsuro
Published: July 2015

Significance

The juvenile–adult transition is a key developmental process in organisms. A long-held paradigm in insect endocrinology is that juvenile hormones (JHs) prevent metamorphosis until larvae attain an appropriate size for the juvenile–adult transition. However, little is known about the roles for JHs during embryonic and very early larval stages. We established knockouts of the silkworm, a classic model insect, and show that embryogenesis and maintenance of juvenile status during the early larval stages are largely independent of JHs or the JH-signaling pathway. Our results also suggest that an unidentified factor or signal is required to acquire the competence for metamorphosis. The presence of this factor has long been overlooked because JHs may conceal its action.
The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions
Authors: Tapmeier Thomas T. , Moshnikova Anna , Beech John , Allen Danny , Kinchesh Paul , Smart Sean , Harris Adrian , McIntyre Alan , Engelman Donald M. , Andreev Oleg A. , Reshetnyak Yana K. , Muschel Ruth J.
Published: July 2015

Significance

Acidic pH may distinguish aggressive from more indolent cancers. The limitation on testing this hypothesis to date has been the difficulty of measuring acidic pH in cancers. Here we show that retention of the pH low insertion peptide (pHLIP) Variant 3 (Var3) reflects acidic pH. Using pHLIP Var3, we show its ability to detect cancer with a low false-positive rate in a genetically engineered model of murine breast cancer, paving the way for testing this probe in clinical situations.
Norbin ablation results in defective adult hippocampal neurogenesis and depressive-like behavior in mice
Authors: Wang Hong , Warner-Schmidt Jennifer , Varela Santiago , Enikolopov Grigori , Greengard Paul , Flajolet Marc
Published: July 2015

Significance

G protein-coupled receptors constitute an important class of receptors and represent a family of choice for therapeutic interventions for multiple diseases and disorders. One of these metabotropic glutamate receptors, mGluR5, is highly relevant because of its biological importance for various medical conditions, including major depressive disorder (MDD). In a search of mGluR5 modulators we identified Norbin as a key regulator. Here we demonstrate in vivo that Norbin significantly influences hippocampal neurogenesis and that both the proliferation and survival of newborn neurons are impaired in the absence of Norbin. Furthermore, the use of three well-established behavioral paradigms indicated that Norbin-KO mice display depressive-like characteristics. Thus interventions that could boost Norbin function might be beneficial to treat MDD symptoms.
Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord
Authors: Wang Yuxuan , Springer Simeon , Zhang Ming , McMahon K. Wyatt , Kinde Isaac , Dobbyn Lisa , Ptak Janine , Brem Henry , Chaichana Kaisorn , Gallia Gary L. , Gokaslan Ziya L. , Groves Mari L. , Jallo George I. , Lim Michael , Olivi Alessandro , Quinones-Hinojosa Alfredo , Rigamonti Daniele , Riggins Greg J. , Sciubba Daniel M. , Weingart Jon D. , Wolinsky Jean-Paul , Ye Xiaobu , Oba-Shinjo Sueli Mieko , Marie Suely K. N. , Holdhoff Matthias , Agrawal Nishant , Diaz Luis A. , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Bettegowda Chetan
Published: July 2015

Significance

Outcomes for individuals with central nervous system (CNS) malignancies remain abysmal. A major challenge in managing these patients is the lack of reliable biomarkers to monitor tumor dynamics. Consequently, many patients undergo invasive surgical procedures to determine disease status or experience treatment delays when radiographic testing fails to show disease progression. We show here that primary CNS malignancies shed detectable levels of tumor DNA into the surrounding cerebrospinal fluid (CSF), which could serve as a sensitive and exquisitely specific marker for quantifying tumor burden without invasive biopsies. Therefore, assessment of such tumor-derived DNA in the CSF has the potential to improve the management of patients with primary CNS tumors.
Replacing SNAP-25b with SNAP-25a expression results in metabolic disease
Authors: Valladolid-Acebes Ismael , Daraio Teresa , Brismar Kerstin , Harkany Tibor , Ögren Sven Ove , Hökfelt Tomas G. M. , Bark Christina
Published: July 2015

Significance

Our changed lifestyle, including decreased physical activity and increased food consumption, is leading to a pandemic of obesity and type 2 diabetes, the metabolic syndrome. Impaired release of hormones, such as insulin, from excitable cells usually is considered a symptom, not a cause, of this syndrome. Here, however, we show that a small genetic modification, replacing synaptosomal-associated protein of 25 kDa (SNAP-25), SNAP-25b with SNAP-25a in the machinery mediating stimulus-dependent release of hormones and neurotransmitters is sufficient to provoke hypothalamic dysfunction, obesity, and type 2 diabetes. When combined with a Western diet, this genetic condition triggers severe diabesity. Our work expands previous knowledge supporting the notion that many individuals have an increased susceptibility to developing metabolic disease because of a genetic predisposition.
Prospective isolation of human erythroid lineage-committed progenitors
Authors: Mori Yasuo , Chen James Y. , Pluvinage John V. , Seita Jun , Weissman Irving L.
Published: July 2015

Significance

We have identified the first step of erythrocyte lineage commitment in human bone marrow as a CD71intermediate/+CD105+cell fraction of a previously defined megakaryocyte/erythrocyte progenitor population. This purification could be a useful tool for studying physiological and pathological red blood cell development, and should be analyzed in patients suffering from anemia or erythrocytosis such as in myelodysplastic syndrome or polycythemia vera.