bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient genome engineering in human pluripotent stem cells using Cas9 from
Neisseria meningitidis
Authors: Hou Zhonggang , Zhang Yan , Propson Nicholas E. , Howden Sara E. , Chu Li-Fang , Sontheimer Erik J. , Thomson James A.
Published: August 2013

Significance

Genome engineering in human pluripotent stem cells holds great promise for biomedical research and regenerative medicine, but it is very challenging. Recently, an RNA-guided nuclease system called clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) has been applied to genome engineering, greatly increasing the efficiency of genome editing. Here, using a CRISPR-Cas system identified in
Neisseria meningitidis
, which is distinct from the commonly used
Streptococcus pyogenes
system, we demonstrate efficient genome engineering in human pluripotent stem cells. Our study could have a tremendous impact in regenerative medicine.
Patterns of Population Structure Vary Across the Range of the White Sturgeon
Authors: Schreier A. Drauch , Mahardja B. , May B.
Published: August 2013

Critical unknowns surrounding the basic biology of White Sturgeon Acipenser transmontanus have hindered management and conservation efforts. Population genetic data may be used to address some of these uncertainties, but previous examinations of population structure in White Sturgeon have been limited by the highly duplicated nature of the species’ genome. We report results from an analysis of White Sturgeon population structure within and among drainages using 13 polysomic microsatellite loci. Genetic diversity levels varied widely among regions, and the lowest levels were observed in the endangered Kootenai River Distinct Population Segment and the highest levels were detected in regions with access to estuarine and marine habitat. Patterns of within‐drainage population structure varied, and no structure was detected in the Sacramento–San Joaquin drainage and a complex pattern of isolation by distance was revealed in the Columbia–Snake River drainage. These results contrast a previously published evaluation of a White Sturgeon population structure in the Fraser River, which revealed several genetically distinct populations within a single drainage. Examination of population structure among drainages, including from samples collected across the species range, revealed six populations. Populations in the Sacramento–San Joaquin, Kootenai, lower Fraser, and upper Fraser River drainages were distinct. The complex isolation‐by‐distance pattern discovered in the within‐drainage analysis of the Columbia–Snake River drainage was supported by the among‐drainage population structure analysis. Our results provide little support for the practice of managing each impounded reach of the Columbia–Snake River system as a genetically distinct population as adjacent reaches show little to no genetic divergence in these analyses. Variation in patterns of population structure across the species range indicates that the scale of spawning site fidelity for White Sturgeon varies regionally, which has implications for recruitment failure mitigation.
The Effects of Semichronic Thermal Stress on Physiological Indicators in Steelhead
Authors: Kammerer Brittany D. , Heppell Scott A.
Published: August 2013

The physiological response of juvenile steelhead Oncorhynchus mykiss to prolonged heat stress was examined by exposing replicated groups of fish to three different temperatures, 15, 23, and 25°C, for 25 consecutive days followed by a 55‐d recovery period at 15°C. We found that at temperatures ≥ 25°C, steelhead consumed significantly less food per day and had elevated feed conversion rates but experienced slower growth, reduced body size, lower body fat, and elevated heat shock protein (hsp) 70 levels relative to fish exposed to 23°C and 15°C. Growth decreased 24.4% and 27.1% for length and mass, respectively, between 15°C and 23°C, and an additional 60% and 56.5%, respectively, between 23°C and 25°C during exposures. While growth increments and lipid levels recovered to control levels after water temperature was reduced, body size of the fish exposed to 25°C lagged throughout the experiment. Our results indicate a temperature threshold after which steelhead exposed to semichronic thermal stress incur a physiological debt. Heat shock protein 70 levels were detectable up to 25 d poststress in fin and liver tissues. This result provides evidence that hsp 70 is a useful metric for measuring thermal stress that can be assessed nonlethally and used to monitor thermal‐habitat restoration efforts for threatened and endangered salmonids.
Pathologic and Physiologic Effects Associated with Long-Term Intracoelomic Transmitters in Captive Siberian Sturgeon
Authors: Boone S. Shaun , Divers Stephen J. , Camus Alvin C. , Peterson Douglas L. , Jennings Cecil A. , Shelton James L. , Hernandez Sonia M.
Published: August 2013

Intracoelomic transmitters are commonly used to evaluate migratory patterns, distribution, and habitat use of many species of fish. Currently, transmitter implantation relies mostly on the assumption that transmitters do not cause any adverse physiological or pathological effects on the animal. To investigate these effects, we surgically implanted 60 Siberian Sturgeon Acipenser baeri with transmitters that weighed less than 2% of their body weight. Postoperative assessments were conducted at 1, 2, 8, 12, 26, and 55 weeks to evaluate surgical healing and transmitter retention. Blood samples were collected before and after the 55-week study for serum cortisol analysis. Overall transmitter loss was 32%. Minor to moderate adhesions were noted at necropsy but did not appear to affect organ function. One fish was noted to have an intraintestinal transmitter at necropsy, but the fish was in overall good health. Long-term transmitter presence does not appear to increase serum cortisol levels or affect overall growth more than nontransmitter fish. Although long-term telemetry studies can be undertaken with minimal concern for negative physiological or pathological effects from transmitters, researchers should be aware that transmitter loss rates may be higher than previously thought. Mechanisms for transmitter loss may include expulsion through the surgical incision, expulsion through the mucocutaneous junction between the large intestine and the vent, or intraintestinal capture and expulsion through the vent.

Received February 10, 2013; accepted June 10, 2013
Geopolitical shifts: Asia rising, America declining in the Middle East?
Authors: Hudson Michael C.
Published: August 2013

This paper explores the implications of the tectonic shifts in the global balance of power marked by the rise of China and India and the relative decline of American hegemony across the Indian Ocean region – bordered as it is by five continents and some 40 countries. Located at the Middle Eastern end of it are the strategic chokepoints of the Bab al-Mandab and the Strait of Hormuz, and at the Asian end the Strait of Malacca. However, while the Middle East and Asia are ever more interconnected across this third-largest ocean (and also along the reviving terrestrial ‘Silk Road’) through trade, finance and culture, the paper does not foresee an imminent confrontation in the Middle East between the rising Asian superpowers and the United States. Nonetheless, it is contended that President Barack Obama’s dramatic ‘rebalancing’ project indicates that America intends to intensify its support for the small Asian states worried about China’s assertiveness in the East and South China seas, while at the same time insisting that this ‘pivot’ does not mean a diminution of US power in the Middle East. For the time being, it seems that China and India are content to remain ‘free riders’ in the Middle East, uninterested in challenging the United States.
Relationship between state and religion in Saudi Arabia: the role of Wahabism in governance
Authors: Alsaif Tawfiq
Published: August 2013

This paper tracks the relationship between religion and the state in Saudi Arabia during the past 50 years. This relationship is unique in the sense that the religious power (Wahabi) together with the ruling family (Al Sa’ud) were partners in founding the Kingdom. This cooperative relationship has been degenerating into mutual suspicion. Right now there are three main variants of religious stratification in Saudi Arabia vis-à-vis the state: the traditional Salafists who back the rulers come what may – the government is gradually reducing their prerogatives; and the opposition, which in turn is divided between Sahwa (who are discontented Salafists) and Tanweeris (advocates of enlightenment). The Sahwa current with its elderly leadership believes that the state is straying away from the teachings of religion and it recommends austere adherence to it; the dynamics of their activities are possibly pushing towards taking leadership from outside the Kingdom. The Tanweeris, on the other hand, have young leaders, the popular base is young and broad, and they are strong advocates of democracy. Despite their capacity for effective social mobilization, it seems too early to judge whether this religious stream will eventually push for reform or constrain it, especially given that it has not yet resolved its position on some key issues such as different national constituencies and women.
Multicolor fate mapping of Langerhans cell homeostasis
Authors: Ghigo Clément , Mondor Isabelle , Jorquera Audrey , Nowak Jonathan , Wienert Stephan , Zahner Sonja P. , Clausen Björn E. , Luche Hervé , Malissen Bernard , Klauschen Frederick , Bajénoff Marc
Published: August 2013

Langerhans cells (LCs) constitute a network of immune sentinels in the skin epidermis that is seeded during embryogenesis. Whereas the development of LCs has been extensively studied, much less is known about the homeostatic renewal of adult LCs in “nonmanipulated” animals. Here, we present a new multicolor fluorescent fate mapping system and quantification approach to investigate adult LC homeostasis. This novel approach enables us to propose and provide evidence for a model in which the adult epidermal LC network is not formed by mature coequal LCs endowed with proliferative capabilities, but rather constituted by adjacent proliferative units composed of “dividing” LCs and their terminally differentiated daughter cells. Altogether, our results demonstrate the general utility of our novel fate-mapping system to follow cell population dynamics in vivo and to establish an alternative model for LC homeostasis.
Committed Procurement in Privately Negotiated Markets: Evidence from Laboratory Markets
Authors: Sabasi Darlington M. , Bastian Christopher T. , Menkhaus Dale J. , Phillips Owen R.
Published: August 2013

Previous research suggests an increase in committed procurement can result in lower cash market prices for livestock. There is a paucity of research that ascertains prices received by market agents trading in a prior bargaining session via alternative marketing arrangements versus those who have not. We use laboratory market experiments to analyze the potential impacts of committed procurement on privately negotiated transactions when some traders have two windows of negotiation and others have one. Results illustrate that those who do not engage in prior trading are at a bargaining disadvantage due to matching and inventory loss risks.
European Pediatricians' Approach to Children With GER Symptoms
Authors: Quitadamo Paolo , Papadopoulou Alexandra , Wenzl Tobias , Urbonas Vaidotas , Kneepkens C.M. Frank , Roman Enriqueta , Orel Rok , Pavkov Danijela Jojkić , Dias Jorge Amil , Vandenplas Yvan , Kostovski Aco , Miele Erasmo , Villani Alberto , Staiano Annamaria
Published: August 2013

Objective:

The aim of this study was to evaluate the current implementation of the 2009 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition‐European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines, and to assess proton pump inhibitors' (PPIs) prescribing patterns among pediatricians from different European countries.

Methods:

A randomly identified sample of general pediatricians distributed across 11 European countries. They were asked to complete a case report–structured questionnaire investigating their approaches to infants, children, and adolescents with symptoms suggestive of gastroesophageal reflux.

Results:

A total of 567 European general pediatricians completed the study questionnaire. Only 1.8% of them showed complete adherence to the guidelines. Forty‐six percent of them reported that they diagnose gastroesophageal reflux disease based on clinical symptoms irrespective of the age of the child; 39% prescribe PPIs in infants with unexplained crying and/or distressed behavior and 36% prescribe PPIs in infants with uncomplicated recurrent regurgitation and vomiting; 48% prescribed PPIs in children younger than 8 to 12 years with vomiting and heartburn, without specific testing; 45% discontinue PPI therapy abruptly rather than tapering the dose. The overall rate of pediatricians overprescribing PPIs was 82%.

Conclusions:

The overall results of our survey show that the majority of pediatricians are unaware of 2009 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition‐European Society for Pediatric Gastroenterology, Hepatology, and Nutrition reflux guidelines and often prescribe PPIs despite a lack of efficacy for the symptoms being treated. The overdiagnosis of gastroesophageal reflux disease places undue burden on both families and national health systems, which has not been affected by the publication of international guidelines.
Ultrasonographic Predictors of Esophageal Varices
Authors: de Alcantara Roberta V. , Yamada Roberto M. , Cardoso Sílvia R. , de Fátima Maria , Servidoni C.P. , Hessel Gabriel
Published: August 2013

Objective:

The aim of this study was to identify ultrasonographic predictors of esophageal varices (EVs) in children and adolescents with chronic liver disease (CLD) and extrahepatic portal venous obstruction (EHPVO).

Methods:

This study evaluates 53 patients younger than 20 years with CLD or EHPVO and no history of bleeding or prophylactic EVs treatment. They were divided into 2 groups: group I (35 with CLD) and group II (18 with EHPVO). Splenorenal shunt (SS), gallbladder wall varices, gallbladder wall thickening (GT), and lesser omental thickness (LOT) were compared with the presence of EVs, gastric varices, and portal hypertensive gastropathy (PHG). Univariate (χ2 test, Fisher exact test, and Wilcoxon signed rank test) and multivariate (logistic regression) analyses were performed. The area under the receiver operating curve was calculated.

Results:

EVs were observed in 48.5% of patients with CLD and in 83.3% of patients with EHPVO. SS (P = 0.0329) and LOT (P = 0.0151) predicted EV among patients with CLD. A median of 5.3 mm of LOT was considered a predictor of EVs among these patients. Multivariate analysis showed SS as an independent predictor of EVs in patients with EHPVO (odds ratio 15). Gallbladder varices (P = 0.0245) and GT (P = 0.0289) predicted EVs among patients with EHPVO. PHG occurred more often among patients with CLD who had SS (P = 0.0384) and greater LOT (P = 0.0226).

Conclusions:

SS and a greater LOT were indicative of EV among children and adolescents with CLD. Gallbladder varices and GT were indicative of EVs among patients with EHPVO. SS and a greater LOT were indicative of PHG among patients with CLD.
On the concept and elucidation of endogenous retroviruses
Authors: Weiss Robin A.
Published: August 2013

Endogenous retrovirus (ERV) genomes integrated into the chromosomal DNA of the host were first detected in chickens and mice as Mendelian determinants of Gag and Env proteins and of the release of infectious virus particles. The presence of ERV was confirmed by DNA hybridization. With complete host genomes available for analysis, we can now see the great extent of viral invasion into the genomes of numerous vertebrate species, including humans. ERVs are found at many loci in host DNA and also in the genomes of large DNA viruses, such as herpesviruses and poxviruses. The evolution of xenotropism and cross-species infection is discussed in the light of the dynamic relationship between exogenous and endogenous retroviruses.
Host gene evolution traces the evolutionary history of ancient primate lentiviruses
Authors: Compton Alex A. , Malik Harmit S. , Emerman Michael
Published: August 2013

Simian immunodeficiency viruses (SIVs) have infected primate species long before  human immunodeficiency virus has infected humans. Dozens of species-specific lentiviruses are found in African primate species, including two strains that have repeatedly jumped into human populations within the past century. Traditional phylogenetic approaches have grossly underestimated the age of these primate lentiviruses. Instead, here we review how selective pressures imposed by these viruses have fundamentally altered the evolutionary trajectory of hosts genes and, even in cases where there now remains no trace of the viruses themselves, these evolutionary signatures can reveal the types of viruses that were once present. Examination of selection by ancient viruses on the adaptive evolution of host genes has been used to derive minimum age estimates for modern primate lentiviruses. This type of data suggests that ancestors of modern SIV existed in simian primates more than 10 Ma. Moreover, examples of host resistance and viral adaptation have implications not only for estimating the age and host range of ancient primate lentiviruses, but also the pathogenic potential of their modern counterparts.
Functional endogenous viral elements in the genome of the parasitoid wasp
Cotesia congregata
: insights into the evolutionary dynamics of bracoviruses
Authors: Bézier Annie , Louis Faustine , Jancek Séverine , Periquet Georges , Thézé Julien , Gyapay Gabor , Musset Karine , Lesobre Jérome , Lenoble Patricia , Dupuy Catherine , Gundersen-Rindal Dawn , Herniou Elisabeth A. , Drezen Jean-Michel
Published: August 2013

Bracoviruses represent the most complex endogenous viral elements (EVEs) described to date. Nudiviral genes have been hosted within parasitoid wasp genomes since approximately 100 Ma. They play a crucial role in the wasp life cycle as they produce bracovirus particles, which are injected into parasitized lepidopteran hosts during wasp oviposition. Bracovirus particles encapsidate multiple dsDNA circles encoding virulence genes. Their expression in parasitized caterpillars is essential for wasp parasitism success. Here, we report on the genomic organization of the proviral segments (i.e. master sequences used to produce the encapsidated dsDNA circles) present in the
Cotesia congregata
parasitoid wasp genome. The provirus is composed of a macrolocus, comprising two-thirds of the proviral segments and of seven dispersed loci, each containing one to three segments. Comparative genomic analyses with closely related species gave insights into the evolutionary dynamics of bracovirus genomes. Conserved synteny in the different wasp genomes showed the orthology of the proviral macrolocus across different species. The nudiviral gene
odv-e66-like1
is conserved within the macrolocus, suggesting an ancient co-localization of the nudiviral genome and bracovirus proviral segments. By contrast, the evolution of proviral segments within the macrolocus has involved a series of lineage-specific duplications.
Myroides guanonis sp. nov., isolated from prehistoric paintings
Authors: Tomova Anna , Tomova Iva , Vasileva-Tonkova Evgenia , Lazarkevich Irina , Stoilova-Disheva Margarita , Lyutskanova Dimitrinka , Kambourova Margarita
Published: August 2013

A novel psychrotolerant, strictly aerobic, non-motile, rod-shaped bacterial strain, designated IM13T, was isolated from a sample taken from prehistoric guano paintings in Magura Cave, northwest Bulgaria and subjected to a polyphasic taxonomic study. Strain IM13T formed yellow colonies on LB agar plates and was Gram-staining-negative, heterotrophic and alkalitolerant. It grew optimally at pH 7.5 and 30 °C in the absence of NaCl. Phylogenetic analysis of the whole 16S rRNA gene revealed that strain IM13T branched with representatives of the genus

Myroides

with sequence similarity of 93–94 % with other species of the genus. The novel isolate contained iso-C15 : 0 (49.1 %), iso-C17 : 1ω9c (18.2 %) and iso-C17 : 0 3-OH (14.0 %) as dominant fatty acids. The DNA G+C content of strain IM13T was 33.5 mol%. Based on phylogenetic inference and phenotypic characteristics, it was concluded that strain IM13T represents a novel species of the genus

Myroides

, for which the name Myroides guanonis sp. nov. is proposed. The type strain is IM13T ( = DSM 26542T = NBIMCC 8736T).
Rhodotorula portillonensis sp. nov., a basidiomycetous yeast isolated from Antarctic shallow-water marine sediment
Authors: Laich Federico , Vaca Inmaculada , Chávez Renato
Published: August 2013

During the characterization of the mycobiota associated with shallow-water marine environments from Antarctic sea, a novel pink yeast species was isolated. Sequence analysis of the D1/D2 domain of the LSU rDNA gene and 5.8S-ITS regions revealed that the isolated yeast was closely related to Rhodotorula pallida CBS 320T and Rhodotorula benthica CBS 9124T. On the basis of morphological, biochemical and physiological characterization and phylogenetic analyses, a novel basidiomycetous yeast species, Rhodotorula portillonensis sp. nov., is proposed. The type strain is Pi2T ( = CBS 12733T  = CECT 13081T) which was isolated from shallow-water marine sediment in Fildes Bay, King George Island, Antarctica.
Kurtzmanomyces shapotouensis sp. nov., an anamorphic, basidiomycetous yeast isolated from desert soil crusts
Authors: Zhang Tao , Jia Rong-Liang , Zhang Yu-Qin , Liu Hong-Yu , Su Jing , Yu Li-Yan
Published: August 2013

Two yeast strains isolated from soil crusts in the Shapotou region of Tengger Desert (north-western China) were grouped in the genus Kurtzmanomyces based on morphological characteristics. rRNA gene sequence analyses (including the D1/D2 domain of the large subunit rRNA gene and internal transcribed spacer region) indicated that these two strains represented a novel species of the genus Kurtzmanomyces, for which the name Kurtzmanomyces shapotouensis sp. nov. is proposed (type strain: CPCC 300020T = DSM 26579T = CBS 12707T). The MycoBank number of the novel species is MB 804959.
DNA–DNA hybridization study of strains of Chryseobacterium, Elizabethkingia and Empedobacter and of other usually indole-producing non-fermenters of CDC groups IIc, IIe, IIh and IIi, mostly from human clinical sources, and proposals of Chryseobacterium bernardetii sp. nov., Chryseobacterium carnis sp. nov., Chryseobacterium lactis sp. nov., Chryseobacterium nakagawai sp. nov. and Chryseobacterium taklimakanense comb. nov.
Authors: Holmes B. , Steigerwalt A. G. , Nicholson A. C.
Published: August 2013

The taxonomic classification of 182 phenotypically similar isolates was evaluated using DNA–DNA hybridization and 16S rRNA gene sequence analysis. These bacterial isolates were mainly derived from clinical sources; all were Gram-negative non-fermenters and most were indole-producing. Phenotypically, they resembled species from the genera

Chryseobacterium

,

Elizabethkingia

or

Empedobacter

or belonged to CDC groups IIc, IIe, IIh and IIi. Based on these analyses, four novel species are described: Chryseobacterium bernardetii sp. nov. (type strain NCTC 13530T = CCUG 60564T = CDC G229T), Chryseobacterium carnis sp. nov. (type strain NCTC 13525T = CCUG 60559T = CDC G81T), Chryseobacterium lactis sp. nov. (type strain NCTC 11390T = CCUG 60566T = CDC KC1864T) and Chryseobacterium nakagawai sp. nov. (type strain NCTC 13529T = CCUG 60563T = CDC G41T). The new combination Chryseobacterium taklimakanense comb. nov. (type strain NCTC 13490T = X-65T = CCTCC AB 208154T = NRRL B-51322T) is also proposed to accommodate the reclassified Planobacterium taklimakanense.
Nibribacter koreensis gen. nov., sp. nov., isolated from estuarine water
Authors: Kang Ji Young , Chun Jeesun , Jahng Kwang Yeop
Published: August 2013

A Gram-reaction-negative, rod-shaped, non-motile, red-pigmented bacterium, designated strain GSR3061T, was isolated from a water sample of the Mangyung estuary enclosed by the Saemangeum Embankment in JEOLlabuk-do of South Korea, and characterized using a polyphasic approach. 16S rRNA gene sequence analysis of strain GSR3061Tindicated that the isolate belonged to the phylumBacteroidetesand exhibited similarity levels of 94.7 % toRufibacter tibetensisNRRL B-51285T, 92.4 % toAdhaeribacter terreusKACC 14257Tand 91.9 % toPontibacter korlensisKACC 15371T. Growth was observed at 15–40 °C and pH 6.5–9.5. The major cellular fatty acids of the novel strain were summed feature 4 (comprising iso-C17 : 1I and/or anteiso-C17 : 1B), iso-C15 : 0, C17 : 1ω6cand iso-C16 : 1H. Flexirubin-type pigments were absent. The DNA G+C content of strain GSR3061Twas 44.9 mol% and the major quinone was MK-7. The polar lipid profile consisted mainly of phosphatidylethanolamine; three unidentified lipids, two unknown aminolipids, two unknown phospholipids, an unknown aminophospholipid and an unknown glycolipid were also present. On the basis of the evidence presented, it is concluded that strain GSR3061Trepresents a novel species of a new genus, for which the nameNibribacter koreensisgen. nov., sp. nov. is proposed. The type strain ofNibribacter koreensisis GSR3061T( = KACC 16450T = JCM 17917T).
Cisplatin causes cell death via TAB1 regulation of p53/MDM2/MDMX circuitry
Authors: Zhu Yan , Regunath Kausik , Jacq Xavier , Prives Carol
Published: August 2013

The interdependence of p53 and MDM2 is critical for proper cell survival and cell death and, when altered, can lead to tumorigenesis. Mitogen-activated protein kinase (MAPK) signaling pathways function in a wide variety of cellular processes, including cell growth, migration, differentiation, and death. Here we discovered that transforming growth factor β-activated kinase 1 (TAK1)-binding protein 1 (TAB1), an activator of TAK1 and of p38α, associates with and inhibits the E3 ligase activity of MDM2 toward p53 and its homolog, MDMX. Depletion of TAB1 inhibits MDM2 siRNA-mediated p53 accumulation and p21 induction, partially rescuing cell cycle arrest induced by MDM2 ablation. Interestingly, of several agents commonly used as DNA-damaging therapeutics, only cell death caused by cisplatin is mitigated by knockdown of TAB1. Two mechanisms are required for TAB1 to regulate apoptosis in cisplatin-treated cells. First, p38α is activated by TAB1 to phosphorylate p53 N-terminal sites, leading to selective induction of p53 targets such as NOXA. Second, MDMX is stabilized in a TAB1-dependent manner and is required for cell death after cisplatin treatment. Interestingly TAB1 levels are relatively low in cisplatin-resistant clones of ovarian cells and in ovarian patient's tumors compared with normal ovarian tissue. Together, our results indicate that TAB1 is a potential tumor suppressor that serves as a functional link between p53–MDM2 circuitry and a key MAPK signaling pathway.
Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape
Authors: Shah Parisha P. , Donahue Greg , Otte Gabriel L. , Capell Brian C. , Nelson David M. , Cao Kajia , Aggarwala Varun , Cruickshanks Hazel A. , Rai Taranjit Singh , McBryan Tony , Gregory Brian D. , Adams Peter D. , Berger Shelley L.
Published: August 2013

Senescence is a stable proliferation arrest, associated with an altered secretory pathway, thought to promote tumor suppression and tissue aging. While chromatin regulation and lamin B1 down-regulation have been implicated as senescence effectors, functional interactions between them are poorly understood. We compared genome-wide Lys4 trimethylation on histone H3 (H3K4me3) and H3K27me3 distributions between proliferating and senescent human cells and found dramatic differences in senescence, including large-scale domains of H3K4me3- and H3K27me3-enriched “mesas” and H3K27me3-depleted “canyons.” Mesas form at lamin B1-associated domains (LADs) in replicative senescence and oncogene-induced senescence and overlap DNA hypomethylation regions in cancer, suggesting that pre-malignant senescent chromatin changes foreshadow epigenetic cancer changes. Hutchinson-Gilford progeria syndrome fibroblasts (mutant lamin A) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence. Canyons mostly form between LADs and are enriched in genes and enhancers. H3K27me3 loss is correlated with up-regulation of key senescence genes, indicating a link between global chromatin changes and local gene expression regulation. Lamin B1 reduction in proliferating cells triggers senescence and formation of mesas and canyons. Our data illustrate profound chromatin reorganization during senescence and suggest that lamin B1 down-regulation in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging, and cancer.
Jasmonate Regulates the INDUCER OF CBF EXPRESSION–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 Cascade and Freezing Tolerance in Arabidopsis
Authors: Hu Yanru , Jiang Liqun , Wang Fang , Yu Diqiu
Published: August 2013

The INDUCER OF CBF EXPRESSION (ICE)–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several JASMONATE ZIM-DOMAIN (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance.
2-[Anilino(diphenylphosphoryl)methyl]phenol from a three-component Kabachnik–Fields reaction
Authors: Wu Ming-Shu , Feng Qing-Qin , Li Gao-Nan , Wan De-Hui
Published: August 2013

The title compound, C25H22NO2P, was synthesized in high yield by a three-component Kabachnik–Fields reaction of diphenylphosphine oxide, salicylaldehyde and aniline in dry toluene at room temperature. It precipitates as racemic crystals, in which strong hydrogen bonds between the hydroxy group and the P=O group of a neighbouring molecule form one-dimensional heterochiral chains along the crystallographicaaxis, with an O...O separation of 2.568 (2) Å. The pseudo-tetrahedral environment of the P atom is distorted, with O—P—C bond angles significantly larger than the C—P—C angles.
Haploinsufficiency of endogenous parathyroid hormone‐related peptide impairs bone fracture healing
Authors: Wang Yin‐He , Qiu Yong , Han Xiao‐Dong , Xiong Jin , Chen Yi‐Xin , Shi Hong‐Fei , Karaplis Andrew
Published: August 2013

Previous studies have demonstrated that endogenous parathyroid hormone‐related peptide (PTHrP) plays a central role in the physiological regulation of bone formation. However, it is unclear whether endogenous PTHrP plays an important function in enhancing bone fracture healing.

To determine whether endogenous PTHrP haploinsufficiency impaired bone fracture healing, closed mid‐diaphyseal femur fractures were created in 8‐week‐old wild‐type and Pthrp+/− mice. Callus tissue properties were analysed 1, 2 and 4 weeks after fracture by radiography, histology, histochemistry, immunohistochemistry and molecular biology.

The size of the calluses was reduced 2 weeks after fracture, and the fracture repairs were poor 4 weeks after fractures, in Pthrp+/− compared with wild‐type mice. Cartilaginous callus areas were reduced 1 week after fracture, but were increased 2 weeks after fracture in Pthrp+/− mice. There was a reduction in the number of ostoblasts, alkaline phosphatase (ALP)‐positive areas, Type I collagen immunopositive areas, mRNA levels of ALP, Runt‐related transcription factor 2 (Runx2) and Type I collagen, Runx2 and insulin‐like growth factor‐1 protein levels, the number of osteoclasts and the surface in callus tissues in Pthrp+/− compared with wild‐type mice.

These results demonstrate that endogenous PTHrP haploinsufficiency impairs the fracture repair process by reducing cartilaginous and bony callus formation, with downregulation of osteoblastic gene and protein expression and a reduction in endochondral bone formation, osteoblastic bone formation and osteoclastic bone resorption. Together, the results indicate that endogenous PTHrP plays an important role in fracture healing.
Morphological and molecular marker contributions to disentangling the cryptic Hermeuptychia hermes species complex (Nymphalidae: Satyrinae: Euptychiina)
Authors: Seraphim N. , Marín M. A. , Freitas A. V. L. , Silva‐Brandão K. L.
Published: August 2013

The genus Hermeuptychia is common and widespread through the Americas, from Argentina to the southern United States of America. All eight recognized species within Hermeuptychia are small and brown, with very similar interspecific external morphologies and intraspecifically variable ocelli patterns that render taxonomic identification based on morphology difficult. In our study, we surveyed variability within Hermeuptychia, and evaluated species boundaries based on molecular data (sequences of the ‘barcode’ mitochondrial DNA COI gene) and morphology (mainly male genitalia), using a phylogenetic approach. We found eight DNA‐based and 12 morphological groups in our sampling. Species names were assigned based mainly on comparisons with male genitalia morphology descriptions corresponding to name‐bearing type specimens. Morphological and DNA variability were highly congruent, with the exception of group H, the Hermeuptychia cucullina complex. Also, the barcode region showed a clear threshold for intra‐ and interspecific mean distances around 2%. Based on these results, we circumscribe the species boundaries in the genus Hermeuptychia and discuss conflicts between mitochondrial genes and classic morphological approaches for identifying and delimiting species. Our study revealed cryptic diversity within an ubiquitous genus of Neotropical butterflies.
Object processing for action across childhood
Authors: Dekker Tessa M. , Mareschal Denis
Published: August 2013

Human adults process and select the opportunities for action in their environment rapidly, efficiently, and effortlessly. While several studies have revealed substantial improvements in object recognition skills, motor abilities, and control over the motor system during late childhood, surprisingly little is known about how object processing for action develops during this period. This study addresses this issue by investigating how the ability to ignore actions potentiated by a familiar utensil develops between ages 6 and 10 years. It is the first study to demonstrate that (1) the mechanisms that transform a graspable visual stimulus into an object‐appropriate motor response are in place by the sixth year of life and (2) graspable features of an object can facilitate and interfere with manual responses in an adult‐like manner by this age. The results suggest that there may be distinct developmental trajectories for the ability to ignore motor responses triggered by visual affordances and the stimulus response compatibility effects typically assessed with Simon tasks.
Dai, David Yun ed (2012) Design research on learning and thinking in educational settingsRoutledge (New York & London) isbn 978‐0‐415‐88051‐0 299 pp £32.99 http://www.routledge.com/books/details/9780415880510/
Authors: Dettori Giuliana
Published: August 2013

This rich and very interesting book, addressed to professionals and graduate students interested in educational innovation, investigates the creation of optimal learning conditions and how these can support personal and context resources. This is to help learners achieve not only content knowledge and competence but also a favourable disposition to learn and to make use of higher‐order thinking skills. If the content of this book is likely to be relevant to your research and development, I recommend that you borrow a copy to study.

Giuliana Dettori
McGreal, Rory et al ed (2013) Open educational resources: Innovation, research and practiceCommonwealth of learning (Vancouver) isbn 978‐1‐894975‐62‐9 239 pp CDN$12 (free pdf or e‐book) http://www.col.org/resources/publications/Pages/detail.aspx?PID=446
Authors: Cannell Pete
Published: August 2013

A timely and wide ranging look at the developing world of Open Educational Resources (oer), with contributions that will be valuable for academics, developers and anyone wishing to gain an informed overview of the field. If you believe the content of this book may well be be relevant to you, I suggest that you borrow a copy to study.

Pete Cannell
Rose, Ellen (2013) On reflectionCanadian Scholars' Press (Toronto) isbn 978‐1‐551‐30518‐9 124 pp $29.95 www.cspi.org/books/reflection
Authors: Cowan John
Published: August 2013

Ellen Rose sets out to initiate deep thinking about what reflection is and should be. She achieves that in an elegantly written, highly readable and thought‐provoking treasure‐trove of scholarly writing. This should be essential reading for those who value reflection and reflective activity. Readers will rejoice in having their thinking on the subject deepened by this exceptional thinker. If you are intrigued by the content of this book, I recommend you purchase a copy for your own use.

John Cowan
Molecular Dynamics Simulation of Chemokine Receptors in Lipid Bilayer: A Case Study on C–C Chemokine Receptor Type 2
Authors: Shahlaei Mohsen , Fassihi Afshin , Papaleo Elena , Pourfarzam Morteza
Published: August 2013

Chemokine receptors belong to the membrane proteins that are included in many physiological phenomena. However, the mechanism of their action is unknown at the atomistic level in different aspects. In this study, a computational pipeline is exploited to investigate the molecular basis of how the structure of C–C chemokine receptor type 2, a prototypical chemokine receptor, is affected by lipid bilayer and an antagonist (INCB3344). This study includes homology modeling, molecular dynamics simulation in lipid bilayer, and docking. A detailed mechanism of INCB3344 has been described. Tyr 49, Trp 98, Tyr 120, His 121, and Glu 291 are proved to play important roles in binding. Integrating results obtained in this study and experimental data help us to suggest a two‐step ligand‐binding mechanism. The N‐terminus of protein first sticks out from the extracellular domain suitable for the contact with the antagonist. Binding of ligand to this segment leads to the geometrical changes to facilitate the ligand interactions with extracellular loop 2 of C–C chemokine receptor type 2. Finally, the interactions occurring between extracellular loop 2 and ligand induce conformational changes in C–C chemokine receptor type 2 structure. These changes bring the ligand closer to the binding pocket, allowing the interaction between INCB3344 and the residues of active site.
Optimization of Compound Ranking for Structure‐Based Virtual Ligand Screening Using an Established FRED–Surflex Consensus Approach
Authors: Du Jiangfeng , Bleylevens Ivo W. M. , Bitorina Albert V. , Wichapong Kanin , Nicolaes Gerry A. F.
Published: August 2013

The use of multiple target conformers has been applied successfully in virtual screening campaigns; however, a study on how to best combine scores for multiple targets in a hierarchic method that combines rigid and flexible docking is not available. In this study, we used a data set of 59 479 compounds to screen multiple conformers of four distinct protein targets to obtain an adapted and optimized combination of an established hierarchic method that employs the programs FRED and Surflex. Our study was extended and verified by application of our protocol to ten different data sets from the directory of useful decoys (DUD). We quantitated overall method performance in ensemble docking and compared several consensus scoring methods to improve the enrichment during virtual ligand screening. We conclude that one of the methods used, which employs a consensus weighted scoring of multiple target conformers, performs consistently better than methods that do not include such consensus scoring. For optimal overall performance in ensemble docking, it is advisable to first calculate a consensus of FRED results and use this consensus as a sub‐data set for Surflex screening. Furthermore, we identified an optimal method for each of the chosen targets and propose how to optimize the enrichment for any target.
The Goal Circuit Model: A Hierarchical Multi‐Route Model of the Acquisition and Control of Routine Sequential Action in Humans
Authors: Cooper Richard P. , Ruh Nicolas , Mareschal Denis
Published: August 2013

Human control of action in routine situations involves a flexible interplay between (a) task‐dependent serial ordering constraints; (b) top‐down, or intentional, control processes; and (c) bottom‐up, or environmentally triggered, affordances. In addition, the interaction between these influences is modulated by learning mechanisms that, over time, appear to reduce the need for top‐down control processes while still allowing those processes to intervene at any point if necessary or if desired. We present a model of the acquisition and control of goal‐directed action that goes beyond existing models by operationalizing an interface between two putative systems—a routine and a non‐routine system—thereby demonstrating how explicitly represented goals can interact with the emergent task representations that develop through learning in the routine system. The gradual emergence of task representations offers an explanation for the transfer of control with experience from the non‐routine goal‐based system to the routine system. At the same time it allows action selection to be sensitive both to environmental triggers and to biasing from multiple levels within the goal system.
Population‐based studies of brain imaging patterns in cerebral palsy
Authors: Reid Susan M , Dagia Charuta D , Ditchfield Michael R , Carlin John B , Reddihough Dinah S
Published: August 2013

Aim

The aim of this study was to review the distribution of neuroimaging findings from a contemporary population cohort of individuals with cerebral palsy (CP) and to facilitate standardization of imaging classification.

Method

Publications from 1995 to 2012 reporting imaging findings in population cohorts were selected through a literature search, and review of the titles, abstracts, and content of studies. Relevant data were extracted, including unpublished data from Victoria, Australia. The proportions for each imaging pattern were tabulated, and heterogeneity was assessed for all individuals with CP, and for subgroups based on gestational age, CP subtype, and Gross Motor Function Classification System level.

Results

Studies from three geographic regions met the inclusion criteria for individuals with CP, and two additional studies reported on specific CP subtypes. Brain abnormalities were observed in 86% of scans, but were observed least often in children with ataxia (24–57%). White matter injury was the most common imaging pattern (19–45%), although the proportions showed high heterogeneity. Additional patterns were grey matter injury (21%), focal vascular insults (10%), malformations (11%), and miscellaneous findings (4–22%).

Interpretation

This review suggests areas where further dialogue will facilitate progress towards standardization of neuroimaging classification. Standardization will enable future collaborations aimed at exploring the relationships among magnetic resonance imaging patterns, risk factors, and clinical outcomes, and, ultimately, lead to better understanding of causal pathways and opportunities for prevention.
Using the Assisting Hand Assessment and the Mini‐AHA for clinical evaluation and further research and development
Authors: Bower Eva
Published: August 2013

This commentary is on the original article by Greaves et al. on pages 1030–1037 of this issue.
Employment outcomes for adults with cerebral palsy: an issue that needs to be addressed
Authors: Vogtle Laura K
Published: August 2013

This commentary is on the original article by Huang et al. on pages 1000–1008 of this issue.
Left Ventricular Mass and Hypertrophy by Echocardiography and Cardiac Magnetic Resonance: The Multi‐Ethnic Study of Atherosclerosis
Authors: Armstrong Anderson C. , Gjesdal Ola , Almeida André , Nacif Marcelo , Wu Colin , Bluemke David A. , Brumback Lyndia , Lima João A. C.
Published: August 2013

Background

Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk.

Methods

Multi‐Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height1.7, height2.7, or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland–Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities.

Results

Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76.

Conclusions

Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
Unique Sail‐Like Structure of Cor Triatriatum Dexter in Three‐Dimensional Echocardiogram
Authors: Low Ting Ting , Uy Celia Catherine C. , Wong Raymond Ching Chiew
Published: August 2013

Cor triatriatum dexter (CTD) is an extremely rare congenital condition arising from the persistence of the right valve of the sinus venosus. It divides the right atrium (RA) into 2 separate chambers. We report a case of a 50‐year‐old man who had an incidental finding of CTD on transesophageal echocardiogram. An incomplete membrane of the RA was seen, and three‐dimensional echocardiogram delineated the structure clearly as a triangular sail‐like structure with multiple orifices and a fenestration.