bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome
Authors: Castro Jorge , Garcia Rodrigo I. , Kwok Showming , Banerjee Abhishek , Petravicz Jeremy , Woodson Jonathan , Mellios Nikolaos , Tropea Daniela , Sur Mriganka
Published: June 2014

Significance

Rett Syndrome is a devastating neurodevelopmental disorder that arises from mutations in the methyl-CpG binding protein 2 (MeCP2) gene and has no presently available treatment. We show that levels of insulin-like growth factor-1 (IGF1) are reduced in male and femaleMecp2mutant mice. Treating male knockout mice with recombinant human IGF1 (rhIGF1) improves a range of physiological symptoms and behaviors, increases excitatory transmission and synapse density in cortical neurons, and up-regulates molecular signals underlying these deficits. Treating symptomatic female heterozygous mice also improves a range of physiological and behavioral symptoms and normalizes maturation of cortical circuits. These findings demonstrate that rhIGF1 corrects functional, structural, and molecular mechanisms downstream of MeCP2 and may be an effective therapeutic for Rett Syndrome.
Actin-binding protein 1 links B-cell antigen receptors to negative signaling pathways
Authors: Seeley-Fallen Margaret K. , Liu Lisa J. , Shapiro Melanie R. , Onabajo Olusegun O. , Palaniyandi Senthilkumar , Zhu Xiaoping , Tan Tse-Hua , Upadhyaya Arpita , Song Wenxia
Published: June 2014

Significance

B cells are the major mediators of humoral immunity, producing antibody to aid in the elimination of pathogens. B cells signal through their membrane receptors, resulting in transcriptional modification for the maintenance of B-cell survival, proliferation, and antibody production. B-cell receptor (BCR) signaling is tightly regulated, and elevated or sustained BCR signals lead to loss of B-cell tolerance and subsequent autoimmunity. This study reveals that the adaptor molecule Abp1 negatively regulates development of marginal zone and spontaneous germinal center B cells, as well as autoantibody production. As a link between the actin cytoskeleton and BCR signaling, Abp1 assists BCR signal attenuation by promoting BCR central cluster formation, as well as recruitment of inhibitory signaling molecules to BCR signalosomes.
Archean komatiite volcanism controlled by the evolution of early continents
Authors: Mole David R. , Fiorentini Marco L. , Thebaud Nicolas , Cassidy Kevin F. , McCuaig T. Campbell , Kirkland Christopher L. , Romano Sandra S. , Doublier Michael P. , Belousova Elena A. , Barnes Stephen J. , Miller John
Published: June 2014

Significance

Komatiites are rare, ultra-high-temperature (∼1,600 °C) lavas that were erupted in large volumes 3.5–1.5 bya but only very rarely since. They are the signature rock type of a hotter early Earth. However, the hottest, most extensive komatiites have a very restricted distribution in particular linear belts within preserved Archean crust. This study used a combination of different radiogenic isotopes to map the boundaries of Archean microcontinents in space and time, identifying the microplates that form the building blocks of Precambrian cratons. Isotopic mapping demonstrates that the major komatiite belts are located along these crustal boundaries. Subsequently, the evolution of the early continents controlled the location and extent of major volcanic events, crustal heat flow, and major ore deposit provinces.
Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons
Authors: Ohno Nobuhiko , Chiang Hao , Mahad Don J. , Kidd Grahame J. , Liu LiPing , Ransohoff Richard M. , Sheng Zu-Hang , Komuro Hitoshi , Trapp Bruce D.
Published: June 2014

Significance

Degeneration of demyelinated axons is a major cause of permanent neurological disability in primary diseases of myelin. In addition to myelin loss, dysfunction of axonal mitochondria may be an essential requisite for degeneration of demyelinated axons. Here we describe a significant increase in axonal mitochondrial volume following demyelination of CNS axons. A deficiency in tethering mitochondria to the cytoskeleton prevented this volume increase in demyelinated axons and increased axonal degeneration, which was rescued by pharmacological inhibition of nerve transmission along the demyelinated axon. These results demonstrate that (
i
) increasing mitochondrial volume in CNS demyelinated axons protects against axonal degeneration and (
ii
) immobilization of mitochondria is required for the increase in axonal mitochondria volume following CNS demyelination.
C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis
Authors: Collins Cailin , Wang Jingya , Miao Hongzhi , Bronstein Joel , Nawer Humaira , Xu Tao , Figueroa Maria , Muntean Andrew G. , Hess Jay L.
Published: June 2014

Significance

Acute myeloid leukemia (AML) is a highly heterogeneous form of cancer that results from the uncontrolled proliferation of primitive immune cells. Homeobox A9 (HOXA9) is an evolutionarily conserved transcription factor that is overexpressed in a large percentage of AML cases and is associated with a poor prognosis. Here, we show that CCAAT/enhancer binding protein alpha (C/EBPα), a transcription factor involved in immune cell development that is commonly mutated in AML, is a critical collaborator required for HOXA9-mediated leukemic transformation. We also establish that the cell cycle regulator cyclin-dependent kinase inhibitors
Cdkn2a/b
are corepressed by the Hoxa9–C/EBPα complex. These findings suggest a novel functional interaction between two leukemic transcription factors, HOXA9 and C/EBPα, that is altered in a large percentage of AML cases.
Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation
Authors: Kissick Haydn T. , Sanda Martin G. , Dunn Laura K. , Pellegrini Kathryn L. , On Seung T. , Noel Jonathan K. , Arredouani Mohamed S.
Published: June 2014

Significance

Testosterone has been implicated as a regulator of the immune response to viruses, vaccines, host tissue, and cancer. Despite this pleiotropic effect on the immune system, the mechanisms underlying this effect are not well understood. In this study, we investigated how testosterone altered gene expression and signaling mechanisms in CD4 T cells in mouse models and prostate cancer patients undergoing androgen deprivation therapy. We found that testosterone inhibited T-helper 1 differentiation by up-regulating the phosphatase,
Ptpn1
, in both mice and humans. Additionally, the androgen receptor bound a highly conserved region of the Ptpn1 gene, suggesting an evolutionarily important purpose of this mechanism. This study provides a mechanism to explain recent discoveries regarding the role of testosterone-mediated inhibition of the immune response.
Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in
Arabidopsis
Authors: Para Alessia , Li Ying , Marshall-Colón Amy , Varala Kranthi , Francoeur Nancy J. , Moran Tara M. , Edwards Molly B. , Hackley Christopher , Bargmann Bastiaan O. R. , Birnbaum Kenneth D. , McCombie W. Richard , Krouk Gabriel , Coruzzi Gloria M.
Published: June 2014

Significance

Cellular signals evoke rapid and broad changes in gene regulatory networks. To uncover these network dynamics, we developed an approach able to monitor primary targets of a transcription factor (TF) based solely on gene regulation, in the absence of detectable binding. This enabled us to follow the transient propagation of a nitrogen (N) nutrient signal as a direct impact of the master TF Basic Leucine Zipper 1 (bZIP1). Unexpectedly, the largest class of primary targets that exhibit transient associations with bZIP1 is uniquely relevant to the rapid and dynamic propagation of the N signal. Our ability to uncover this transient network architecture has revealed the “dark matter” of dynamic N nutrient signaling in plants that has previously eluded detection.
Water resources transfers through Chinese interprovincial and foreign food trade
Authors: Dalin Carole , Hanasaki Naota , Qiu Huanguang , Mauzerall Denise L. , Rodriguez-Iturbe Ignacio
Published: June 2014

Significance

China’s fast socioeconomic growth increasingly strains national water resources, notably through rising urbanization and meat demand. Agriculture is located mainly in the dry north, where irrigation largely relies on groundwater reserves. This paper analyzes the role of international and interprovincial food trade in China’s national agricultural water-use and food supply. We combine a hydrological model with a trade model to quantify the volumes of irrigation and rainfall water transferred between provinces and other countries through agricultural trade. We find that China’s dry, irrigation-intensive provinces tend to export food commodities to wetter places, and identify specific provinces and products showing high potential for irrigation productivity enhancements. These findings are essential to inform sound policies aimed at improving agricultural sustainability in China.
Dissipative self-assembly of particles interacting through time-oscillatory potentials
Authors: Tagliazucchi Mario , Weiss Emily A. , Szleifer Igal
Published: June 2014

Significance

Dissipative self-assembly is the organization of a system requiring continuous input of energy to the system from its environment. Dissipative self-assembly is ubiquitous in biology, where it leads to structures unavailable in equilibrium conditions and to complex dynamical behavior. There are, however, only a few synthetic examples of this phenomenon. This work proposes a method for dissipative self-assembly through the oscillations of the interaction potentials. As an example, a mixture of pH-responsive particles subjected to fast pH oscillations self-assembles into different nonequilibrium structures that cannot be obtained in equilibrium at fixed pH. This result shows that nontrivial dissipative structures can be formed by periodic oscillation of the forces among particles and reveals a novel strategy to create far-from-equilibrium self-organized structures.
STAT1-induced ASPP2 transcription identifies a link between neuroinflammation, cell polarity, and tumor suppression
Authors: Turnquist Casmir , Wang Yihua , Severson David T. , Zhong Shan , Sun Bin , Ma Jingyi , Constantinescu Stefan N. , Ansorge Olaf , Stolp Helen B. , Molnár Zoltán , Szele Francis G. , Lu Xin
Published: June 2014

Significance

Two of the most debilitating and scientifically challenging diseases of the 21st century are cancer and neurodegeneration. Although cancer results from excessive cell growth, neurodegeneration is a consequence of excessive cell loss. Dysfunction of the same key regulators, including oncogenes and tumor suppressors, may cause both diseases. We report that LPS and IFN induce apoptosis-stimulating protein of p53 with signature sequences of ankyrin repeat-, SH3 domain-, and proline-rich region-containing protein 2 (ASPP2) transcription through a signal transducer and activator of transcription 1 (STAT1) -dependent but NF-κB RELA/p65-independent pathway and that ASPP2 mediates LPS-induced apoptosis. Thus, the identified STAT1/ASPP2 pathway reveals an important function of ASPP2 in the cellular response to inflammation and infection and connects neuroinflammation to cell polarity and tumor suppression.
When recognition memory is independent of hippocampal function
Authors: Smith Christine N. , Jeneson Annette , Frascino Jennifer C. , Kirwan C. Brock , Hopkins Ramona O. , Squire Larry R.
Published: June 2014

Significance

Hippocampal damage has been thought to impair memory for all domains of material (sounds, objects, words, odors). We investigated face recognition memory in patients with hippocampal lesions or large medial temporal lobe lesions. Recognition of novel faces was unequivocally intact in hippocampal patients but only at a short retention interval. Recognition memory for words, buildings, famous faces, and inverted faces was impaired. For medial temporal lobe patients, memory was impaired in all conditions. Ordinarily, recognition memory judgments depend on an association between study items and the study context. We suggest that face memory is spared because face processing is specialized (and holistic), and that participants can make recognition judgments without making explicit reference to the study context.
Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration
Authors: Rinkevich Yuval , Montoro Daniel T. , Muhonen Ethan , Walmsley Graham G. , Lo David , Hasegawa Masakazu , Januszyk Michael , Connolly Andrew J. , Weissman Irving L. , Longaker Michael T.
Published: June 2014

Significance

In Urodeles, surgical denervation before limb amputation results in regeneration failure. Here we explored the dependency of the peripheral nervous system on tissue replacement in mammalian appendages by performing a comprehensive clonal analysis of hind limb tissues devoid of nerve supply. Our experiments uncover conserved phenotypes, which mimic clinical observations of patients with nerve damage resulting from spinal cord injury. Our system could be used to better understand both pathophysiology and treatment of patients with spinal cord injury.
A Patient Navigation Intervention for Drug-Involved Former Prison Inmates
Authors: Binswanger Ingrid A. , Whitley Elizabeth , Haffey Paul-Ryan , Mueller Shane R. , Min Sung-Joon
Published: June 2014

Background: Former prison inmates experience high rates of hospitalizations and death during the transition from prison to the community, particularly from drug-related causes and early after release. The authors designed a randomized controlled trial (RCT) of patient navigation to reduce barriers to health care and hospitalizations for former prison inmates. Methods: Forty former prison inmates with a history of drug involvement were recruited and randomized within 15 days after prison release. Participants were randomized to receive 3 months of patient navigation (PN) with facilitated enrollment into an indigent care discount program (intervention) or facilitated enrollment into an indigent care discount program alone (control). Structured interviews were conducted at baseline, 3 months, and 6 months. Outcomes were measured as a change in self-reported barriers to care and as the rate of health service use per 100 person-days. Results: The mean number of reported barriers to care was reduced at 3 and 6 months in both groups. At 6 months, the rate of emergency department/urgent care visits per 100 person-days since baseline was 1.1 among intervention participants and 0.5 among control participants ( P = .04), whereas the rate of hospitalizations per 100 person-days was 0.2 in intervention participants and 0.6 in control participants ( P = .04). Conclusions: Recruitment of former inmates into an RCT of patient navigation was highly feasible, but follow-up was limited by rearrests. Results suggest a significantly lower rate of hospitalizations among navigation participants, although the rate of emergency department/urgent care visits was not improved. Patient navigation is a promising, pragmatic intervention that may be effective at reducing high-cost health care utilization in former prison inmates.
A genomic search approach to identify carbonyl reductases in Gluconobacter oxydans for enantioselective reduction of ketones
Authors: Chen Rong , Liu Xu , Lin Jinping , Wei Dongzhi
Published: June 2014

The versatile carbonyl reductases from Gluconobacter oxydans in the enantioselective reduction of ketones to the corresponding alcohols were exploited by genome search approach. All purified enzymes showed activities toward the tested ketoesters with different activities. In the reduction of 4-phenyl-2-butanone with in situ NAD(P)H regeneration system, (S)-alcohol was obtained with an e.e. of up to 100% catalyzed by Gox0644. Under the same experimental condition, all enzymes catalyzed ethyl 4-chloroacetoacetate to give chiral products with an excellent e.e. of up to 99%, except Gox0644. Gox2036 had a strict requirement for NADH as the cofactor and showed excellent enantiospecificity in the synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate. For the reduction of ethyl 2-oxo-4-phenylbutyrate, excellent e.e. (>99%) and high conversion (93.1%) were obtained by Gox0525, whereas the other enzymes showed relatively lower e.e. and conversions. Among them, Gox2036 and Gox0525 showed potentials in the synthesis of chiral alcohols as useful biocatalysts.
Posture-based processing in visual short-term memory for actions
Authors: Vicary Staci A. , Stevens Catherine J.
Published: June 2014

Visual perception of human action involves both form and motion processing, which may rely on partially dissociable neural networks. If form and motion are dissociable during visual perception, then they may also be dissociable during their retention in visual short-term memory (VSTM). To elicit form-plus-motion and form-only processing of dance-like actions, individual action frames can be presented in the correct or incorrect order. The former appears coherent and should elicit action perception, engaging both form and motion pathways, whereas the latter appears incoherent and should elicit posture perception, engaging form pathways alone. It was hypothesized that, if form and motion are dissociable in VSTM, then recognition of static body posture should be better after viewing incoherent than after viewing coherent actions. However, as VSTM is capacity limited, posture-based encoding of actions may be ineffective with increased number of items or frames. Using a behavioural change detection task, recognition of a single test posture was significantly more likely after studying incoherent than after studying coherent stimuli. However, this effect only occurred for spans of two (but not three) items and for stimuli with five (but not nine) frames. As in perception, posture and motion are dissociable in VSTM.
Proapoptotic Bim regulates antigen-specific NK cell contraction and the generation of the memory NK cell pool after cytomegalovirus infection
Authors: Min-Oo Gundula , Bezman Natalie A. , Madera Sharline , Sun Joseph C. , Lanier Lewis L.
Published: June 2014

Apoptosis is critical for the elimination of activated lymphocytes after viral infection. Proapoptotic factor Bim (Bcl2l11) controls T lymphocyte contraction and the formation of memory T cells after infection. Natural killer (NK) cells also undergo antigen-driven expansion to become long-lived memory cells after mouse cytomegalovirus (MCMV) infection; therefore, we examined the role of Bim in regulating the MCMV-driven memory NK cell pool. Despite responding similarly early after infection, Bcl2l11−/− Ly49H+ NK cells show impaired contraction and significantly outnumber wild-type (WT) cells after the expansion phase. The inability to reduce the effector pool leads to a larger Bcl2l11−/− NK memory subset, which displays a less mature phenotype (CD11blo, CD27+) and lower levels of NK cell memory-associated markers KLRG1 and Ly6C. Bcl2l11−/− memory NK cells demonstrate a reduced response to m157-mediated stimulation and do not protect as effectively as WT memory NK cells in an MCMV challenge model. Thus, Bim-mediated apoptosis drives selective contraction of effector NK cells to generate a pool of mature, MCMV-specific memory cells.
The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation
Authors: Rodgers Mary A. , Bowman James W. , Fujita Hiroaki , Orazio Nicole , Shi Mude , Liang Qiming , Amatya Rina , Kelly Thomas J. , Iwai Kazuhiro , Ting Jenny , Jung Jae U.
Published: June 2014

Linear ubiquitination is a newly discovered posttranslational modification that is currently restricted to a small number of known protein substrates. The linear ubiquitination assembly complex (LUBAC), consisting of HOIL-1L, HOIP, and Sharpin, has been reported to activate NF-κB–mediated transcription in response to receptor signaling by ligating linear ubiquitin chains to Nemo and Rip1. Despite recent advances, the detailed roles of LUBAC in immune cells remain elusive. We demonstrate a novel HOIL-1L function as an essential regulator of the activation of the NLRP3/ASC inflammasome in primary bone marrow–derived macrophages (BMDMs) independently of NF-κB activation. Mechanistically, HOIL-1L is required for assembly of the NLRP3/ASC inflammasome and the linear ubiquitination of ASC, which we identify as a novel LUBAC substrate. Consequently, we find that HOIL-1L−/− mice have reduced IL-1β secretion in response to in vivo NLRP3 stimulation and survive lethal challenge with LPS. Together, these data demonstrate that linear ubiquitination is required for NLRP3 inflammasome activation, defining the molecular events of NLRP3 inflammasome activation and expanding the role of LUBAC as an innate immune regulator. Furthermore, our observation is clinically relevant because patients lacking HOIL-1L expression suffer from pyogenic bacterial immunodeficiency, providing a potential new therapeutic target for enhancing inflammation in immunodeficient patients.
A multiobjective method for robust identification of bacterial small non-coding RNAs
Authors: Arnedo Javier , Romero-Zaliz Rocío , Zwir Igor , del Val Coral
Published: June 2014

Motivation: Small non-coding RNAs (sRNAs) have major roles in the post-transcriptional regulation in prokaryotes. The experimental validation of a relatively small number of sRNAs in few species requires developing computational algorithms capable of robustly encoding the available knowledge and using this knowledge to predict sRNAs within and across species.

Results: We present a novel methodology designed to identify bacterial sRNAs by incorporating the knowledge encoded by different sRNA prediction methods and optimally aggregating them as potential predictors. Because some of these methods emphasize specificity, whereas others emphasize sensitivity while detecting sRNAs, their optimal aggregation constitutes trade-off solutions between these two contradictory objectives that enhance their individual merits. Many non-redundant optimal aggregations uncovered by using multiobjective optimization techniques are then combined into a multiclassifier, which ensures robustness during detection and prediction even in genomes with distinct nucleotide composition. By training with sRNAs in Salmonella enterica Typhimurium, we were able to successfully predict sRNAs in Sinorhizobium meliloti , as well as in multiple and poorly annotated species. The proposed methodology, like a meta-analysis approach, may begin to lay a possible foundation for developing robust predictive methods across a wide spectrum of genomic variability.

Availability and implementation: Scripts created for the experimentation are available at http://m4m.ugr.es/SupInfo/sRNAOS/sRNAOSscripts.zip .

Contact:  delval@decsai.ugr.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Resources partitioning by seabirds and their relationship with other consumers at and around a small tropical archipelago
Authors: Mancini Patrícia L. , Bugoni Leandro
Published: June 2014

Seabirds occupy a range of trophic levels in marine foodwebs, and as top predators, they potentially may compete with large fish for prey. Here, we examine trophic segregation among seabird species breeding on São Pedro and São Paulo Archipelago (SPSPA), in the tropical Atlantic Ocean, as well as the trophic relationships between the seabirds and pelagic fish. We used stable isotopes (δ15N, δ13C) combined with a conventional dietary analysis of brown booby (Sula leucogaster), brown noddy (Anous stolidus), and black noddy (Anous minutus) and also analysed stable isotopes in the muscles of tropical two-wing flying fish (Exocoetus volitans), blackfin tuna (Thunnus atlanticus), and common dolphinfish (Coryphaena hippurus). Brown boobies shared a similar trophic level with large predatory fish probably due to their intense consumption of flying fish, but seabirds are most likely not competing with blackfin tuna and common dolphinfish, despite relying on the same prey. Food resources seem to be abundant around SPSPA, minimizing competition. Despite relying mostly on two-wing flying fish, the three seabirds studied had non-overlapping trophic niches during the breeding period, with segregation apparently occurring by prey size. Sex-related trophic differences were not found, but age-related trophic segregation was observed in brown boobies and brown noddies. Overall, although seabirds and marine pelagic fish rely on the same prey species, the overlap in their trophic niches was limited, most likely due to an overabundant food resource, i.e. flying fish, a common prey of large predators in most pelagic tropical oceans.
Celiac Disease Genetics
Authors: Wijmenga Cisca , Gutierrez‐Achury Javier
Published: June 2014

In the past few years there has been enormous progress in unraveling the genetic basis of celiac disease (CD). Apart from the well‐known association to HLA, there are currently 40 genomic loci associated to CD. Most of these loci show pleiotropic effects across many autoimmune diseases and highlight the importance of a dysregulated immune system in the predisposition to CD. It is still too early, however, to use genetics in clinical practice for predicting individual risk. The major challenge for the future is to translate genetic findings into a better understanding of the underlying disease mechanism and to design new ways to treat CD and prevent its development.
Evaluation of genetic isolation within an island flora reveals unusually widespread local adaptation and supports sympatric speciation
Authors: Papadopulos Alexander S. T. , Kaye Maria , Devaux Céline , Hipperson Helen , Lighten Jackie , Dunning Luke T. , Hutton Ian , Baker William J. , Butlin Roger K. , Savolainen Vincent
Published: June 2014

It is now recognized that speciation can proceed even when divergent natural selection is opposed by gene flow. Understanding the extent to which environmental gradients and geographical distance can limit gene flow within species can shed light on the relative roles of selection and dispersal limitation during the early stages of population divergence and speciation. On the remote Lord Howe Island (Australia), ecological speciation with gene flow is thought to have taken place in several plant genera. The aim of this study was to establish the contributions of isolation by environment (IBE) and isolation by community (IBC) to the genetic structure of 19 plant species, from a number of distantly related families, which have been subjected to similar environmental pressures over comparable time scales. We applied an individual-based, multivariate, model averaging approach to quantify IBE and IBC, while controlling for isolation by distance (IBD). Our analyses demonstrated that all species experienced some degree of ecologically driven isolation, whereas only 12 of 19 species were subjected to IBD. The prevalence of IBE within these plant species indicates that divergent selection in plants frequently produces local adaptation and supports hypotheses that ecological divergence can drive speciation in sympatry.
The demography and population genomics of evolutionary transitions to self-fertilization in plants
Authors: Barrett Spencer C. H. , Arunkumar Ramesh , Wright Stephen I.
Published: June 2014

The evolution of self-fertilization from outcrossing has occurred on numerous occasions in flowering plants. This shift in mating system profoundly influences the morphology, ecology, genetics and evolution of selfing lineages. As a result, there has been sustained interest in understanding the mechanisms driving the evolution of selfing and its environmental context. Recently, patterns of molecular variation have been used to make inferences about the selective mechanisms associated with mating system transitions. However, these inferences can be complicated by the action of linked selection following the transition. Here, using multilocus simulations and comparative molecular data from related selfers and outcrossers, we demonstrate that there is little evidence for strong bottlenecks associated with initial transitions to selfing, and our simulation results cast doubt on whether it is possible to infer the role of bottlenecks associated with reproductive assurance in the evolution of selfing. They indicate that the effects of background selection on the loss of diversity and efficacy of selection occur rapidly following the shift to high selfing. Future comparative studies that integrate explicit ecological and genomic details are necessary for quantifying the independent and joint effects of selection and demography on transitions to selfing and the loss of genetic diversity.
Altitudinal gradients, plant hybrid zones and evolutionary novelty
Authors: Abbott Richard J. , Brennan Adrian C.
Published: June 2014

Altitudinal gradients are characterized by steep changes of the physical and biotic environment that present challenges to plant adaptation throughout large parts of the world. Hybrid zones may form where related species inhabit different neighbouring altitudes and can facilitate interspecific gene flow and potentially the breakdown of species barriers. Studies of such hybrid zones can reveal much about the genetic basis of adaptation to environmental differences stemming from changes in altitude and the maintenance of species divergence in the face of gene flow. Furthermore, owing to recombination and transgressive effects, such hybrid zones can be sources of evolutionary novelty. We document plant hybrid zones associated with altitudinal gradients and emphasize similarities and differences in their structure. We then focus on recent studies of a hybrid zone between two
Senecio
species that occur at high and low altitude on Mount Etna, Sicily, showing how adaptation to local environments and intrinsic selection against hybrids act to maintain it. Finally, we consider the potential of altitudinal hybrid zones for generating evolutionary novelty through adaptive introgression and hybrid speciation. Examples of homoploid hybrid species of
Senecio
and
Pinus
that originated from altitudinal hybrid zones are discussed.
Ecological studies of polyploidy in the 100 years following its discovery
Authors: Ramsey Justin , Ramsey Tara S.
Published: June 2014

Polyploidy is a mutation with profound phenotypic consequences and thus hypothesized to have transformative effects in plant ecology. This is most often considered in the context of geographical and environmental distributions—as achieved from divergence of physiological and life-history traits—but may also include species interactions and biological invasion. This paper presents a historical overview of hypotheses and empirical data regarding the ecology of polyploids. Early researchers of polyploidy (1910s–1930s) were geneticists by training but nonetheless savvy to its phenotypic effects, and speculated on the importance of genome duplication to adaptation and crop improvement. Cytogenetic studies in the 1930s–1950s indicated that polyploids are larger (sturdier foliage, thicker stems and taller stature) than diploids while cytogeographic surveys suggested that polyploids and diploids have allopatric or parapatric distributions. Although autopolyploidy was initially regarded as common, influential writings by North American botanists in the 1940s and 1950s argued for the principle role of allopolyploidy; according to this view, genome duplication was significant for providing a broader canvas for hybridization rather than for its phenotypic effectsper se. The emphasis on allopolyploidy had a chilling effect on nascent ecological work, in part due to taxonomic challenges posed by interspecific hybridization. Nonetheless, biosystematic efforts over the next few decades (1950s–1970s) laid the foundation for ecological research by documenting cytotype distributions and identifying phenotypic correlates of polyploidy. Rigorous investigation of polyploid ecology was achieved in the 1980s and 1990s by population biologists who leveraged flow cytometry for comparative work in autopolyploid complexes. These efforts revealed multi-faceted ecological and phenotypic differences, some of which may be direct consequences of genome duplication. Several classical hypotheses about the ecology of polyploids remain untested, however, and allopolyploidy—regarded by most botanists as the primary mode of genome duplication—is largely unstudied in an ecological context.
Tangled up in two: a burst of genome duplications at the end of the Cretaceous and the consequences for plant evolution
Authors: Vanneste Kevin , Maere Steven , Van de Peer Yves
Published: June 2014

Genome sequencing has demonstrated that besides frequent small-scale duplications, large-scale duplication events such as whole genome duplications (WGDs) are found on many branches of the evolutionary tree of life. Especially in the plant lineage, there is evidence for recurrent WGDs, and the ancestor of all angiosperms was in fact most likely a polyploid species. The number of WGDs found in sequenced plant genomes allows us to investigate questions about the roles of WGDs that were hitherto impossible to address. An intriguing observation is that many plant WGDs seem associated with periods of increased environmental stress and/or fluctuations, a trend that is evident for both present-day polyploids and palaeopolyploids formed around the Cretaceous–Palaeogene (K–Pg) extinction at 66 Ma. Here, we revisit the WGDs in plants that mark the K–Pg boundary, and discuss some specific examples of biological innovations and/or diversifications that may be linked to these WGDs. We review evidence for the processes that could have contributed to increased polyploid establishment at the K–Pg boundary, and discuss the implications on subsequent plant evolution in the Cenozoic.
The legacy of diploid progenitors in allopolyploid gene expression patterns
Authors: Buggs Richard J. A. , Wendel Jonathan F. , Doyle Jeffrey J. , Soltis Douglas E. , Soltis Pamela S. , Coate Jeremy E.
Published: June 2014

Allopolyploidization (hybridization and whole-genome duplication) is a common phenomenon in plant evolution with immediate saltational effects on genome structure and gene expression. New technologies have allowed rapid progress over the past decade in our understanding of the consequences of allopolyploidy. A major question, raised by early pioneer of this field Leslie Gottlieb, concerned the extent to which gene expression differences among duplicate genes present in an allopolyploid are a legacy of expression differences that were already present in the progenitor diploid species. Addressing this question necessitates phylogenetically well-understood natural study systems, appropriate technology, availability of genomic resources and a suitable analytical framework, including a sufficiently detailed and generally accepted terminology. Here, we review these requirements and illustrate their application to a natural study system that Gottlieb worked on and recommended for this purpose: recent allopolyploids ofTragopogon(Asteraceae). We reanalyse recent data from this system within the conceptual framework of parental legacies on duplicate gene expression in allopolyploids. On a broader level, we highlight the intellectual connection between Gottlieb's phrasing of this issue and the more contemporary framework ofcis-versustrans-regulation of duplicate gene expression in allopolyploid plants.
Polyploidy-associated genome modifications during land plant evolution
Authors: Jiao Yuannian , Paterson Andrew H.
Published: June 2014

The occurrence of polyploidy in land plant evolution has led to an acceleration of genome modifications relative to other crown eukaryotes and is correlated with key innovations in plant evolution. Extensive genome resources provide for relating genomic changes to the origins of novel morphological and physiological features of plants. Ancestral gene contents for key nodes of the plant family tree are inferred. Pervasive polyploidy in angiosperms appears likely to be the major factor generating novel angiosperm genes and expanding some gene families. However, most gene families lose most duplicated copies in a quasi-neutral process, and a few families are actively selected for single-copy status. One of the great challenges of evolutionary genomics is to link genome modifications to speciation, diversification and the morphological and/or physiological innovations that collectively compose biodiversity. Rapid accumulation of genomic data and its ongoing investigation may greatly improve the resolution at which evolutionary approaches can contribute to the identification of specific genes responsible for particular innovations. The resulting, more ‘particulate’ understanding of plant evolution, may elevate to a new level fundamental knowledge of botanical diversity, including economically important traits in the crop plants that sustain humanity.
Increased expression of capsid protein in trans enhances production of single-round infectious particles by West Nile virus DNA vaccine candidate
Authors: Roby Justin A. , Bielefeldt-Ohmann Helle , Prow Natalie A. , Chang David C. , Hall Roy A. , Khromykh Alexander A.
Published: June 2014

West Nile virus(WNV; genusFlavivirus, familyFlaviviridae) is an emerging pathogenic arbovirus responsible for outbreaks of encephalitis around the world. Whilst no vaccines are currently available to prevent WNV infection of humans, the use of cDNA copies of flavivirus RNA genomes with large internal deletions within the capsid (C) appears promising. C-deleted vaccines are able to replicate and secrete large amounts of non-infectious immunogenic subviral particles (SVPs) from transfected cells. We have previously generated a WNV DNA vaccine candidate pKUNdC/C where C-deleted WNV cDNA was placed under the control of one copy of the cytomegalovirus (CMV) promoter and the C gene was placed under the control of a second copy of the CMV promoter in the same plasmid DNA. This DNA was shown to generate single-round infectious particles (SRIPs) capable of delivering self-replicating C-deleted RNA producing SVPs to surrounding cells, thus enhancing the vaccine potential. However, the amounts of both SRIPs and SVPs produced from pKUNdC/C DNA were relatively low. In this investigation, we aimed at increasing SRIP production by optimizingtrans-C expression via incorporating different forms of C and the use of a more powerful promoter. The construct containing an elongation factor EF1α promoter encoding an extended form of C was demonstrated to produce the highest titres of SRIPs and was immunogenic in mice. Additionally, SRIP and SVP titres were further improved via incorporation of a glycosylation motif in the envelope protein. The optimized DNA yielded ~100-fold greater titres of SRIPs than the original construct, thus providing a promising candidate for further vaccine evaluation.
Spurious peaks arising from multiple scattering events involving the sample environment in inelastic neutron scattering
Authors: Pintschovius Lothar , Reznik Dmitry , Weber Frank , Bourges Philippe , Parshall D. , Mittal Ranjan , Chaplot Samrath Lal , Heid Rolf , Wolf Thomas , Lamago Daniel , Lynn Jeffrey W.
Published: June 2014

Well defined peaks with energies of about 18 meV have been observed in a variety of inelastic neutron scattering experiments on both single crystals and powders, using either the triple-axis or the time-of-flight technique. They can easily be mistaken for signatures of real excitations. It has been found that they are due to multiple scattering events involving primarily the walls of the sample environment. Hence, they are particularly troublesome in experiments using very small samples, as have been used with recently developed high-intensity neutron spectrometers. Measures required to reduce the unwanted scattering to a minimum are also discussed.
A new experimental setup for high-throughput controlled non-photochemical laser-induced nucleation: application to glycine crystallization
Authors: Clair Bertrand , Ikni Aziza , Li Wenjing , Scouflaire Philippe , Quemener Vincent , Spasojević-de Biré Anne
Published: June 2014

Non-photochemical laser-induced nucleation (NPLIN) has been a growing field of study since 1996, and more than 40 compounds including organics, inorganics and proteins have now been probed under various conditions (solvents, laser types, laser beams etc.). The potential advantages of using this technique are significant, in particular polymorphic control. To realize these benefits, the objective is a carefully designed experimental setup and highly controlled parameters, for example temperature and energy density, in order to reduce the uncertainty regarding the origin of nucleation. In this paper, a new experimental setup designed to study NPLIN is reported. After a full technical description of the present setup, the different functionalities of this device will be illustrated through results on glycine. Glycine crystals obtained through NPLIN nucleate at the meniscus and exhibit different morphologies. The nucleation efficiency, as a function of the supersaturation of the solution used and the laser beam energy density, has also been established for a large number of samples, with all other parameters held constant.
Resolution of small-angle neutron scattering with a reflective focusing optic
Authors: Mildner David F. R.
Published: June 2014

A small-angle neutron scattering instrument that uses a reflective focusing optic can achieve smaller values of the scattering vector, and with higher resolution, than the usual pinhole collimation. When the focusing mirror images the source onto the detector, the analytic expression for the resolution is independent of the sample area and is principally determined by the beam divergence incident on the sample, modified by the distance between the optic and the sample. The results are applied to a focusing SANS instrument with axisymmetric mirrors.
The effect of coordinated water on the connectivity of uranium(IV) sulfatex-hydrate: [U(SO4)2(H2O)5]·H2O and [U(SO4)2(H2O)6]·2H2O, and a comparison with other known structures
Authors: Burns Alexander D. , Patrick Brian O. , Lam Anita E. , Dreisinger David
Published: June 2014

Two new solid-state uranium(IV) sulfatex-hydrate complexes (wherexis the total number of coordinated plus solvent waters), namelycatena-poly[[pentaaquauranium(IV)]-di-μ-sulfato-κ4O:O′] monohydrate], {[U(SO4)2(H2O)5]·H2O}n, and hexaaquabis(sulfato-κ2O,O′)uranium(IV) dihydrate, [U(SO4)2(H2O)6]·2H2O, have been synthesized, structurally characterized by single-crystal X-ray diffraction and analyzed by vibrational (IR and Raman) spectroscopy. By comparing these structures with those of four other known uranium(IV) sulfatex-hydrates, the effect of additional coordinated water molecules on their structures has been elucidated. As the number of coordinated water molecules increases, the sulfate bonds are displaced, thus changing the binding mode of the sulfate ligands to the uranium centre. As a result, uranium(IV) sulfatex-hydrate changes from being fully crosslinked in three dimensions in the anhydrous compound, through sheet and chain linking in the tetra- and hexahydrates, to fully unlinked molecules in the octa- and nonahydrates. It can be concluded that coordinated waters play an important role in determining the structure and connectivity of UIVsulfate complexes.
[2,5-Bis(2,2′-bipyridyl-6-yl)-3,4-diazahexa-2,4-diene]dichloridomanganese(II): from a mononuclear compound to a three-dimensional supramolecular framework through C—H...Cl hydrogen bonds and π–π stacking interactions
Authors: Lu Zhengliang , Zhao Yuanchao , Chen Baolian , Huang Ximing , Fan Chunhua
Published: June 2014

The title compound, [MnCl2(C24H20N6)], has been synthesized and characterized based on the multifunctional ligand 2,5-bis(2,2′-bipyridyl-6-yl)-3,4-diazahexa-2,4-diene (L). The MnIIcentre is five-coordinate with an approximately square-pyramidal geometry. TheLligand acts as a tridendate chelating ligand. The mononuclear molecules are bridged into a one-dimensional chain by two C—H...Cl hydrogen bonds. These chains are assembled into a two-dimensional layer through π–π stacking interactions between adjacent uncoordinated bipyridyl groups. Furthermore, a three-dimensional supramolecular framework is attained through π–π stacking interactions between adjacent coordinated bipyridyl groups.
Is ‘Genocide’ an Anachronistic Concept for the Study of Early Modern Mass Killing?
Authors: Kiernan Ben
Published: June 2014

Is it anachronistic to apply the term ‘genocide’, coined in 1943, to ancient or early modern mass killings, even to those that might fit the mid‐twentieth‐ century definition? Historians must analyse actions and events of the pre‐modern era in the context of cultural stipulations discussed at the time, and of knowledge paradigms then available. To assess people's actions by standards understood in that era, it is important to determine whether a pre‐modern understanding of the concept of genocide existed. Long before that term, earlier terms such as ‘general massacre’ conveyed similar meanings, along with four much older, related terms – holocaust, extermination, crimes against humanity, and war crimes – which also conveyed pre‐modern concepts of the crimes involved. This essay traces the historical lineage and usage of those terms in European and transnational contexts, and argues that conceptions of genocide long pre‐dated the coining of the term. Genocide did occur in early modern times, though it was neither normal practice nor universally permitted and often provoked dissent. The essay concludes that a grasp of the concept and its moral implications long preceded both our word for it and its 1950 legal codification as an international crime. The essay then critiques common misunderstandings of that legal definition: that it refers to the crime's effect rather than the perpetrator's intent; that it is too broad for historians to use; that only a state can commit genocide; that it must involve the participation of an entire ethnic group; and that it must be complete, not partial.
Violence on the Fringes: The Virginia (1622) and Amboyna (1623) Massacres
Authors: Games Alison
Published: June 2014

Two events, both labelled massacres by the English who suffered death at the hands of their rivals, took place within the space of a year on opposite sides of the globe and in widely different overseas contexts. The first episode took place in Virginia in March 1622, when Opechancanough and his soldiers killed one‐third of the English colonists in a surprise attack. The second episode transpired in February 1623 in the Spice Islands, when Dutch East India Company officials in Ambon suspected English East India Company employees of conspiring with Japanese soldiers to seize the trading post, interrogated and tried them, and executed twenty‐one men. This episode, known in England by 1624 as the ‘Amboyna massacre’, endured as a meaningful frame of reference well into the eighteenth century. This article explores the particular contexts of each episode and analyses what violence meant to different participants. It investigates how each event became a ‘massacre’ to survivors and to observers in England. In both Virginia and Amboyna, the English were victims, not perpetrators, of violence, and thus these events offer an opportunity to explore how victims of violence deployed their ordeals, in pamphlets, images, plays, and songs, to further their own ends. Labelled as massacres, these two episodes acquired a meaning apart from the actual course of events, helping the English to reassess their overseas goals, to re‐evaluate their prospects and to define themselves anew.