bluuebunny/crossref_metadata_2025 huggingface dataset:
Monophyly of Verbascum (Scrophularieae : Scrophulariaceae): evidence from nuclear and plastid phylogenetic analyses
Authors: Ghahremaninejad Farrokh , Riahi Mehrshid , Babaei Melina , Attar Faride , Behçet Lütfi , Sonboli Ali
Published: March 2015

Verbascum is one of the main genera of Scrophulariaceae, but delimitation and phylogenetic relationships of this genus are unclear and have not yet been studied using DNA sequences. Here, using four selected molecular markers (nrDNA ITS and the plastid spacers trnS/G, psbA-trnH and trnY/T), we present a phylogeny of Verbascum and test previous infrageneric taxonomic hypotheses as well as its monophyly with respect to Scrophularia. We additionally discuss morphological variation and the utility of morphological characters as predictors of phylogenetic relationships. Our results show that while molecular data unambiguously support the circumscription of Verbascum inferred from morphology, they prove to be of limited utility in resolving infrageneric relationships, suggesting that Verbascum ‘s high species diversity is due to rapid and recent radiation. Our work provides phylogenetic estimation of the genus Verbascum using molecular data and can serve as a starting point for future investigations of Verbascum and relatives.
Temperature influences stomatal density and maximum potential water loss through stomata of Dodonaea viscosa subsp. angustissima along a latitude gradient in southern Australia
Authors: Hill Kathryn E. , Guerin Greg R. , Hill Robert S. , Watling Jennifer R.
Published: March 2015

It is well known that physical leaf traits influence leaf functions, and that these traits vary across environmental gradients. Stomata can influence leaf function, with changes in density and size affecting potential water loss, CO2 uptake, and also leaf cooling. Plasticity in stomatal traits occurs in response to environmental factors; however, identifying which factors have the greatest influence is often difficult. We investigated variation in leaf size, stomatal density and size, and potential water loss from open stomata (gwmax), in the Australian native shrub Dodonaea viscosa subsp. angustissima, across a range of environmental factors including temperature, rainfall and CO2. We used herbarium specimens collected across a latitudinal gradient, and also sampled along an elevation gradient in southern Australia. There were significant relationships between mean summer maximum temperature and stomatal density, and gwmax. We found no significant relationships between rainfall or CO2 and the leaf traits we studied. Increased stomatal density at warmer locations may result in an increase in the potential for transpiration, as a means for evaporative cooling. Alternatively, it may enable increased CO2 and nutrient uptake during the short, winter-growing season.
Intermediate morphophysiological dormancy allows for life-cycle diversity in the annual weed, Turgenia latifolia (Apiaceae)
Authors: Nurulla Miregul , Baskin Carol C. , Lu Juan J. , Tan Dun Y. , Baskin Jerry M.
Published: March 2015

Our aim was to determine the seed dormancy-breaking requirements and type of life cycle of Turgenia latifolia in north-western China. At dispersal in July, only 0–9% of the seeds germinated at 5/2°C, 15/2°C, 20/10°C and 25/15°C; thus, 91% of the seeds exhibited physiological dormancy (PD) and 9% were non-dormant. Also, the embryo was underdeveloped and embryo length : seed length ratio increased from 0.38 in fresh seeds to 0.79 at germination. Seeds buried in dry soil at the four temperature regimes for 12 weeks germinated to ≥50% when tested in darkness at 5/2°C, and those buried at 15/2°C and 20/10°C germinated to ≥50% when tested at 15/2°C. Seeds have intermediate complex morphophysiological dormancy (MPD). PD was broken at high and/or low temperatures, but embryo growth was completed only at low temperatures; gibberellic acid (GA3) promoted germination. Seeds buried under natural conditions during summer germinated to ~70% and ~55% at 5/2°C and 15/2°C, respectively, in darkness in autumn. In a germination-phenology study, cumulative germination was ~20% and ~80% in autumn and spring, respectively. Intermediate complex MPD allows the species to behave as a winter annual and as a short-lived summer annual.
Do CO2, temperature, rainfall and elevation influence stomatal traits and leaf width in Melaleuca lanceolata across southern Australia?
Authors: Hill Kathryn E. , Hill Robert S. , Watling Jennifer R.
Published: March 2015

Herbarium specimens and contemporary collections were used to investigate the effects of environment and CO2 concentration on stomatal density, stomatal size, maximum potential water loss through stomata (gwmax) and leaf width of Melaleuca lanceolata Otto in southern Australia. Variation in CO2 had no effect on stomatal size and density, or gwmax of M. lanceolata. In contrast, stomatal density was negatively correlated with annual rainfall and there were significant, positive relationships between both elevation and mean maximum temperature and stomatal density. There was also a positive relationship between gwmax and maximum temperature. Leaf width was negatively correlated with both maximum temperature and elevation. We suggest that the increase in stomatal density and gwmax with increasing maximum temperatures enhances the potential for evaporative cooling of M. lanceolata leaves. It could also allow plants to maximise opportunities for carbon fixation during the sporadic rainfall events that are typical of drier, northern regions. This occurs in conjunction with a narrowing of the leaves in warmer climates and higher elevations, which results in a decrease in the thickness of the boundary layer. This combination of smaller leaves and increased potential for evaporative cooling through increased stomatal density and gwmax would allow the leaf to stay closer to its optimal temperature for photosynthesis.
Comparative proteomic and physiological characterisation of two closely related rice genotypes with contrasting responses to salt stress
Authors: Abdollah Hosseini Seyed , Gharechahi Javad , Heidari Manzar , Koobaz Parisa , Abdollahi Shapour , Mirzaei Mehdi , Nakhoda Babak , Hosseini Salekdeh Ghasem
Published: March 2015

Salinity is a limiting factor affecting crop growth. We evaluated the responses of a salt-tolerant recombinant inbred rice (Oryza sativa L.) line, FL478, and the salt-sensitive IR29. Seedlings were exposed to salt stress and the growth rate was monitored to decipher the effect of long-term stress. At Day 16, IR29 produced lower shoot biomass than FL478. Significant differences for Na+ and K+ concentrations and Na+ : K+ ratios in roots and shoots were observed between genotypes. Changes in the proteomes of control and salt-stressed plants were analysed, identifying 59 and 39 salt-responsive proteins in roots and leaves, respectively. Proteomic analysis showed greater downregulation of proteins in IR29. In IR29, proteins related to pathways involved in salt tolerance (e.g. oxidative stress response, amino acid biosynthesis, polyamine biosynthesis, the actin cytoskeleton and ion compartmentalisation) changed to combat salinity. We found significant downregulation of proteins related to photosynthetic electron transport in IR29, indicating that photosynthesis was influenced, probably increasing the risk of reactive oxygen species formation. The sensitivity of IR29 might be related to its inability to exclude salt from its transpiration stream, to compartmentalise excess ions and to maintain a healthy photosynthetic apparatus during salt stress, or might be because of the leakiness of its roots, allowing excess salt to enter apoplastically. In FL478, superoxide dismutase, ferredoxin thioredoxin reductase, fibre protein and inorganic pyrophosphatase, which may participate in salt tolerance, increased in abundance. Our analyses provide novel insights into the mechanisms behind salt tolerance and sensitivity in genotypes with close genetic backgrounds.
Phosphorus requirements of some selected soil types in the Fiji sugarcane belt
Authors: Goundar M.S. , Morrison R.J. , Togamana C.
Published: March 2015

The availability of phosphorus (P) in soil is perceived to be one of the limiting factors to sustainable sugarcane production in Fiji. The main objective of this research was to ascertain the amount of bioavailable phosphorus in some Fiji sugarcane growing area soils; this will be valuable in improving the determination of the required amount of inorganic fertilizer to be applied to the soil. In this study, twelve different soils were selected from the sugarcane belt of Fiji and phosphorus buffer index (PBI) and phosphorus isotherm experiments were performed. Soil physical and chemical parameters were also measured and Pearson’s correlation tests used to identify patterns. It was found that Oxisols had the highest PBI values ranging from 134 to 170 while Inceptisols had the lowest ranging from 33 to 54. The PBI data followed a similar pattern to the generated isotherm curves of the different soil types. Most interest was in identifying soils with low PBIs as they have greater potential for P leaching through runoff into waterways. Clay content showed a strong positive correlation with PBI (R = 0.76, p ≤ 0.005). There is strong association with phosphorus fixation in soil with increasing levels of Al and Fe in the soil. Phosphorus availability and P fixation varied with soil types.
A procedure for in vitro evaluation of potato varieties using general plant growth parameters
Authors: Michael Patrick S. , Lepatu Davinah
Published: March 2015

Presented in this paper is a procedure in which meristem tips (0.02 mm) of seventeen recently introduced potato varieties from the International Potato Center (IPC) and a local variety (Sequoia) from PNG were micropropagated and evaluated in vitro based on general Plant Growth Parameters (PGP; shoots, roots, leaves, nodes and height). Using this procedure, the study was able to place the tested varieties into three potentially diverse genetic groups. LSD mean separations also showed highly significant differences (p
Enhancing leafy foods’ intake for optimal nutrition and human security in the South Pacific
Authors: Roshni Rita , Prasad Surendra , Bhati Jagdish
Published: March 2015

In the Pacific Island countries (PICs) major nutritional problems are under-nutrition and micronutrient deficiencies due to low dietary intake of leafy foods. Edible leaves of food crops are some of the inexpensive abundant sources of protein, carbohydrate, minerals, vitamins and fibres. In high natural calamity-prone areas, such as PICs, people frequently remain cut-off from the external sources of food for many days and they mainly survive on leafy food material available in their surroundings. This study investigated about what leafy foods are available in Fiji, which of these are commonly consumed by people and which of these are not used. This study is based on primary data obtained by a household sample survey on a structured questionnaire by personal interview method. The study revealed that a rich variety of leafy foods are available and known to people in Fiji. However, out of twenty six leafy foods listed only ten are regularly consumed by majority of the people. A small proportion of households have used up to five leafy foods i.e. underutilization. However, there are several known leafy foods (eleven) which no one has tried i.e. such leafy foods have not been utilized. The respondents reported many constraints in improving their intakes of leafy foods: (i) higher prices of leafy foods in the market; (ii) lack of space to grow own leafy foods in their backyards; (iii) lack of knowledge about how to prepare delicious dishes out of many leafy foods material; (iv) lack of information about the nutritional value of some of the leafy crops. Hence, to popularize the consumption of underutilized or not-utilized local leafy food crops, there is a need to generate more information on nutritional aspects of those leafy food crops and disseminate it to the people.
In vivo screening of salinity tolerance in Giant Swamp Taro (Cyrtosperma merkusii)
Authors: Rao Shiwangni , Taylor Mary , Jokhan Anjeela
Published: March 2015

Giant Swamp Taro (Cyrtosperma merkusii) is a staple food crop in the Pacific, especially in the low lying atoll islands such as Tuvalu and Kiribati. This is owing to its ability to survive under poor soil conditions and harsh environments. However, as a result of the effects of climate change such as sea water inundation and intrusion into the fresh ground water lens, this crop is now under threat. To address this issue an adaption approach was taken whereby, Cyrtosperma merkusii was screened in vivo for salt tolerance. The epistemology followed random selection of two cultivars Ikaraoi and Katutu. These two cultivars were subjected to 0% (0 parts per trillion), 0.5% (5 ppt), 1% (10 ppt), 1.5% (15 ppt) and 2% (20 ppt) of salt in Yates’s advance seedling common potting mix. Both cultivars were able to tolerate salinity levels up-to 5ppt which is significantly more than the salt tolerance in glycophytes of 2.83 ppt. This research provides an insight into the variation of salt tolerance that may exist in C.merkusii gene pool, which can be used to adapt to natural disasters and buffer its impacts.
Evaluation of soil nutrient management practices of taro farmers in Taveuni, Fiji
Authors: Nisha Sofina , Prasad Surendra , Bhati Jagdish
Published: March 2015

There is evidence that the soil health in Taveuni, Fiji is deteriorating over time threatening livelihoods of taro producers. The present study was conducted to understand the soil nutrient management practices followed by taro farmers in Taveuni. The study revealed that the farmers in Taveuni use various organic and chemical fertilizers and various other soil fertility management practices such as mulching, crop rotation with legumes, yagona and agroforestry. The quantity of nitrogen, phosphorous and potash (NPK) applied to taro crop on different types of soils was meager. The study further revealed that there was imbalanced and insufficient use of chemical fertilizers and organic sources of soil nutrients. The main cause of low use of fertilizers was that the farmers in Taveuni do not know the fertility status of their farms as no soil testing was ever done and majority of them are also not fully aware of various low-cost organic methods of maintaining soil fertility of farms.
Integrating ground and satellite-based observations to determine the degree of grassland curing
Authors: Martin Danielle , Chen Tao , Nichols David , Bessell Rachel , Kidnie Susan , Alexander Jude
Published: March 2015

In Australia, the Grassland Fire Danger Index is determined by several inputs including an essential component, the degree of grassland curing, defined as the proportion of senescent material. In the state of Victoria (south-eastern Australia), techniques used for curing assessment have included the use of ground-based observations and the use of satellite imagery. Both techniques alone have inherent limitations. An improved technique has been developed for estimating the degree of curing that entails the use of satellite observations adjusted by observations from the ground. First, a satellite model was developed, named MapVictoria, based on historical satellite and ground-based observations. Second, with use of the new (MapVictoria) satellite model, an integrated model was developed, named the Victorian Improved Satellite Curing Algorithm, combining near-real-time satellite data with weekly observations of curing from the ground. This integrated model was deployed in operations supporting accurate fire danger calculations for grasslands in Victoria in 2013.
Force-induced on-rate switching and modulation by mutations in gain-of-function von Willebrand diseases
Authors: Kim Jongseong , Hudson Nathan E. , Springer Timothy A.
Published: March 2015

Significance

Binding of von Willebrand factor (VWF) to platelets is regulated by hydrodynamic forces in the vasculature. VWF can sense force and can bind when the hydrodynamics change due to bleeding. We show that force application switches the A1 domain in VWF to a second state with faster on-rate for its binding partner on platelets, GPIbα. This provides a physiological mechanism for activating VWF binding to platelets at sites of bleeding. Moreover, force increases the effects of gain-of-function mutations found in von Willebrand disease (VWD) and platelet-type VWD by mechanically stabilizing bond formation and strength.
Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia
Authors: Zhang Rongli , Hess Douglas T. , Qian Zhaoxia , Hausladen Alfred , Fonseca Fabio , Chaube Ruchi , Reynolds James D. , Stamler Jonathan S.
Published: March 2015

Significance

Oxygen delivery by RBC Hb is essential for life. Just three amino acids in Hb are conserved in all mammals and birds, but only two of those are required to carry oxygen. The third, a Cys within the β-chain, βCys93, has been assigned a role in carrying nitric oxide, which mediates vasodilation. However, the physiological importance of RBC-mediated vasoregulation is unknown. We show that blood flow and tissue oxygenation are markedly impaired in mice with a βCys93Ala mutation. The βCys93Ala mutation also results in myocardial ischemia, cardiac decompensation, and enhanced mortality. These findings support a new view of the respiratory cycle wherein, remarkably, RBCs regulate blood flow and (βCys93NO)-Hb is necessary for adequate tissue oxygenation and normal cardiovascular function.
Des serpents en Irlande! Quelques notes à propos du Libellus septem peccatorum mortalium venena eorumque remedia describens qui dicitur Venenum Malachiae
Authors: Cordonnier Rémy
Published: March 2015

Le Venenum Malachiae est un petit traité de la fin du XIIIe siècle, qui s’appuie sur les propriétés des bêtes venimeuses pour transmettre un enseignement moral. Or, s’il a fait l’objet de quelques études par les spécialistes de la littérature moralisante du Moyen Âge, il n’a en revanche pas attiré l’attention des spécialistes de la littérature animalière. Pourtant ce texte n’est pas sans intérêt, tant par la diversité de ses sources, qui saupoudrent de Sénèque et de Cicéron les traditionnels Isidore ou Grégoire le Grand, que par la diversité et la relative rareté littéraire des espèces mentionnées. Mon propos n’est pas ici de développer le thème du venin et du péché associé aux reptiles et aux autres animaux vénéneux, mais simplement d’attirer l’attention des collègues sur ce petit texte dont j’offre ici un bref état de la question agrémenté de remarques plus spécifiques sur les animaux évoqués dans ce texte qui, je l’espère, susciteront la curiosité du lectorat privilégié de Reinardus.
Les aventures avec le lion
Authors: Martina Piero Andrea
Published: March 2015

Dans Huon d’Auvergne, chanson de geste franco-italienne, le héros du poème, au cours de ses aventures, rencontre un lion combattant contre un serpent. Huon sauve le lion, qui lui montre sa gratitude et le suit dans ses péripéties (le sauvetage d’une pucelle, la conversion de royaumes à la foi chrétienne…). L’épisode, qui qualifie Huon de ‘chevalier au lion’, est composé de façon comparable à celui où Yvain rencontre son lion (Chrétien de Troyes, Le Chevalier au lion). L’objet de cette étude est d’analyser la scène de l’amitié reconnaissante du lion dans les textes français qui nous l’ont transmise, afin de montrer les relations qui les unissent et de proposer quelques conclusions concernant la composition et la fortune de ce thème.
Resiliency as a factor protecting youths from risky behaviour: Moderating effects of gender and sport
Authors: Lipowski Mariusz , Lipowska Małgorzata , Jochimek Magdalena , Krokosz Daniel
Published: March 2015

We hypothesised that resiliency may protect adolescents against risky behaviours, and that both the practicing of sports, and gender are moderating variables in relationships between resiliency and risky behaviours. The study included 18‐year‐old pupils from a selection of secondary schools (n = 556). A total of 188 individuals practiced competitive sports and the remaining 368 participants were non‐athletes. The participants were examined with the Resiliency Assessment Scale for Children and Adolescents (SPP‐18) and with a survey containing questions and statements related to high‐risk “experiments with adulthood”. Adolescent athletes showed higher levels of resiliency than their peers. The power of the “Determination and Persistence in Action” effect on “Alcohol” scale differed significantly between male athletes and male non‐athletes. Only in the athletes groups were higher scores on this scale reflected by lower values on the “Drugs” scale. Moreover, it is possible to observe differences in undertaking risky behaviour between male and female athletes. The analysis of risky sexual behaviour suggests that sport is a risk factor for men, and a protective factor for women. These data suggest that consistent prophylactic and psycho‐educative activities, with a special attention to differences between genders, should be provided to all the adolescents, irrespective of their sport performance levels.
A struggle for identity: Georgian Catholics and their monastery in Istanbul
Authors: Natsvlishvili Natia
Published: March 2015

The Congregation of the Immaculate Conception established in 1861 in Istanbul is a milestone in the history of Georgian Catholics. It played a significant role in the construction and maintenance of a Georgian Catholic identity. The founders and members of the Congregation managed to establish themselves as a distinct Catholic community with their traditional rite and native liturgical language. With their ideas and activities, the friars of the Congregation rebuffed those who thought that their Georgianness was compromised by their Catholicism. This article argues that in the late nineteenth and early twentieth centuries they formed a branch of the Georgian nationalism contributing to the consolidation of the nation.
A geometric setting for quantum 𝔬𝔰𝔭(1|2)
Authors: Fan Zhaobing , Li Yiqiang
Published: March 2015

A geometric categorification is given for arbitrary-large-finite- dimensional quotients of quantum

o
s
p

(
1

|

2
)

\mathfrak {osp}(1|2)

and tensor products of its simple modules. The modified quantum

o
s
p

(
1

|

2
)

\mathfrak {osp}(1|2)

of Clark-Wang, a new version in this paper and the modified quantum

s
l

(
2
)

\mathfrak {sl}(2)

are shown to be isomorphic to each other over a field containing

Q

(
v
)

\mathbb Q(v)

and

−
1

\sqrt {-1}

.
Deuring’s mass formula of a Mumford family
Authors: Sheng Mao , Zuo Kang
Published: March 2015

We study the Newton polygon jumping locus of a Mumford family in char

p
p

. Our main result says that, under a mild assumption on

p
p

, the jumping locus consists of only supersingular points and its cardinality is equal to

(

p
r

−
1
)
(
g
−
1
)

(p^r-1)(g-1)

, where

r
r

is the degree of the defining field of the base curve of a Mumford family in char

p
p

and

g
g

is the genus of the curve. The underlying technique is the

p
p

-adic Hodge theory.
Competition between RNA-binding proteins CELF1 and HuR modulates MYC translation and intestinal epithelium renewal
Authors: Liu Lan , Ouyang Miao , Rao Jaladanki N. , Zou Tongtong , Xiao Lan , Chung Hee Kyoung , Wu Jing , Donahue James M. , Gorospe Myriam , Wang Jian-Ying
Published: March 2015

The mammalian intestinal epithelium is one of the most rapidly self-renewing tissues in the body, and its integrity is preserved through strict regulation. The RNA-binding protein (RBP) ELAV-like family member 1 (CELF1), also referred to as CUG-binding protein 1 (CUGBP1), regulates the stability and translation of target mRNAs and is implicated in many aspects of cellular physiology. We show that CELF1 competes with the RBP HuR to modulate MYC translation and regulates intestinal epithelial homeostasis. Growth inhibition of the small intestinal mucosa by fasting in mice was associated with increased CELF1/ Myc mRNA association and decreased MYC expression. At the molecular level, CELF1 was found to bind the 3′-untranslated region (UTR) of Myc mRNA and repressed MYC translation without affecting total Myc mRNA levels. HuR interacted with the same Myc 3′-UTR element, and increasing the levels of HuR decreased CELF1 binding to Myc mRNA. In contrast, increasing the concentrations of CELF1 inhibited formation of the [HuR/ Myc mRNA] complex. Depletion of cellular polyamines also increased CELF1 and enhanced CELF1 association with Myc mRNA, thus suppressing MYC translation. Moreover, ectopic CELF1 overexpression caused G1-phase growth arrest, whereas CELF1 silencing promoted cell proliferation. These results indicate that CELF1 represses MYC translation by decreasing Myc mRNA association with HuR and provide new insight into the molecular functions of RBPs in the regulation of intestinal mucosal growth.
Expression, sorting, and segregation of Golgi proteins during germ cell differentiation in the testis
Authors: Au Catherine E. , Hermo Louis , Byrne Elliot , Smirle Jeffrey , Fazel Ali , Simon Paul H. G. , Kearney Robert E. , Cameron Pamela H. , Smith Charles E. , Vali Hojatollah , Fernandez-Rodriguez Julia , Ma Kewei , Nilsson Tommy , Bergeron John J. M.
Published: March 2015

The molecular basis of changes in structure, cellular location, and function of the Golgi apparatus during male germ cell differentiation is unknown. To deduce cognate Golgi proteins, we isolated germ cell Golgi fractions, and 1318 proteins were characterized, with 20 localized in situ. The most abundant protein, GL54D of unknown function, is characterized as a germ cell–specific Golgi-localized type II integral membrane glycoprotein. TM9SF3, also of unknown function, was revealed to be a universal Golgi marker for both somatic and germ cells. During acrosome formation, several Golgi proteins (GBF1, GPP34, GRASP55) localize to both the acrosome and Golgi, while GL54D, TM9SF3, and the Golgi trafficking protein TMED7/p27 are segregated from the acrosome. After acrosome formation, GL54D, TM9SF3, TMED4/p25, and TMED7/p27 continue to mark Golgi identity as it migrates away from the acrosome, while the others (GBF1, GPP34, GRASP55) remain in the acrosome and are progressively lost in later steps of differentiation. Cytoplasmic HSP70.2 and the endoplasmic reticulum luminal protein-folding enzyme PDILT are also Golgi recruited but only during acrosome formation. This resource identifies abundant Golgi proteins that are expressed differentially during mitosis, meiosis, and postacrosome Golgi migration, including the last step of differentiation.
PRROC: computing and visualizing precision-recall and receiver operating characteristic curves in R
Authors: Grau Jan , Grosse Ivo , Keilwagen Jens
Published: March 2015

Summary: Precision-recall (PR) and receiver operating characteristic (ROC) curves are valuable measures of classifier performance. Here, we present the R-package PRROC, which allows for computing and visualizing both PR and ROC curves. In contrast to available R-packages, PRROC allows for computing PR and ROC curves and areas under these curves for soft-labeled data using a continuous interpolation between the points of PR curves. In addition, PRROC provides a generic plot function for generating publication-quality graphics of PR and ROC curves.

Availability and implementation: PRROC is available from CRAN and is licensed under GPL 3.

Contact: grau@informatik.uni-halle.de
Learning chromatin states with factorized information criteria
Authors: Hamada Michiaki , Ono Yukiteru , Fujimaki Ryohei , Asai Kiyoshi
Published: March 2015

Motivation: Recent studies have suggested that both the genome and the genome with epigenetic modifications, the so-called epigenome, play important roles in various biological functions, such as transcription and DNA replication, repair, and recombination. It is well known that specific combinations of histone modifications (e.g. methylations and acetylations) of nucleosomes induce chromatin states that correspond to specific functions of chromatin. Although the advent of next-generation sequencing (NGS) technologies enables measurement of epigenetic information for entire genomes at high-resolution, the variety of chromatin states has not been completely characterized.

Results: In this study, we propose a method to estimate the chromatin states indicated by genome-wide chromatin marks identified by NGS technologies. The proposed method automatically estimates the number of chromatin states and characterize each state on the basis of a hidden Markov model (HMM) in combination with a recently proposed model selection technique, factorized information criteria. The method is expected to provide an unbiased model because it relies on only two adjustable parameters and avoids heuristic procedures as much as possible. Computational experiments with simulated datasets show that our method automatically learns an appropriate model, even in cases where methods that rely on Bayesian information criteria fail to learn the model structures. In addition, we comprehensively compare our method to ChromHMM on three real datasets and show that our method estimates more chromatin states than ChromHMM for those datasets.

Availability and implementation: The details of the characterized chromatin states are available in the Supplementary information. The program is available on request.

Contact: mhamada@waseda.jp

Supplementary information: Supplementary data are available at Bioinformatics online.
Integration of somatic mutation, expression and functional data reveals potential driver genes predictive of breast cancer survival
Authors: Suo Chen , Hrydziuszko Olga , Lee Donghwan , Pramana Setia , Saputra Dhany , Joshi Himanshu , Calza Stefano , Pawitan Yudi
Published: March 2015

Motivation: Genome and transcriptome analyses can be used to explore cancers comprehensively, and it is increasingly common to have multiple omics data measured from each individual. Furthermore, there are rich functional data such as predicted impact of mutations on protein coding and gene/protein networks. However, integration of the complex information across the different omics and functional data is still challenging. Clinical validation, particularly based on patient outcomes such as survival, is important for assessing the relevance of the integrated information and for comparing different procedures.

Results: An analysis pipeline is built for integrating genomic and transcriptomic alterations from whole-exome and RNA sequence data and functional data from protein function prediction and gene interaction networks. The method accumulates evidence for the functional implications of mutated potential driver genes found within and across patients. A driver-gene score (DGscore) is developed to capture the cumulative effect of such genes. To contribute to the score, a gene has to be frequently mutated, with high or moderate mutational impact at protein level, exhibiting an extreme expression and functionally linked to many differentially expressed neighbors in the functional gene network. The pipeline is applied to 60 matched tumor and normal samples of the same patient from The Cancer Genome Atlas breast-cancer project. In clinical validation, patients with high DGscores have worse survival than those with low scores (P = 0.001). Furthermore, the DGscore outperforms the established expression-based signatures MammaPrint and PAM50 in predicting patient survival. In conclusion, integration of mutation, expression and functional data allows identification of clinically relevant potential driver genes in cancer.

Availability and implementation: The documented pipeline including annotated sample scripts can be found in http://fafner.meb.ki.se/biostatwiki/driver-genes/.

Contact:  yudi.pawitan@ki.se

Supplementary information:  Supplementary data are available at Bioinformatics online.
Proper evaluation of alignment-free network comparison methods
Authors: Yaveroğlu Ömer Nebil , Milenković Tijana , Pržulj Nataša
Published: March 2015

Motivation: Network comparison is a computationally intractable problem with important applications in systems biology and other domains. A key challenge is to properly quantify similarity between wiring patterns of two networks in an alignment-free fashion. Also, alignment-based methods exist that aim to identify an actual node mapping between networks and as such serve a different purpose. Various alignment-free methods that use different global network properties (e.g. degree distribution) have been proposed. Methods based on small local subgraphs called graphlets perform the best in the alignment-free network comparison task, due to high level of topological detail that graphlets can capture. Among different graphlet-based methods, Graphlet Correlation Distance (GCD) was shown to be the most accurate for comparing networks. Recently, a new graphlet-based method called NetDis was proposed, which was claimed to be superior. We argue against this, as the performance of NetDis was not properly evaluated to position it correctly among the other alignment-free methods.

Results: We evaluate the performance of available alignment-free network comparison methods, including GCD and NetDis. We do this by measuring accuracy of each method (in a systematic precision-recall framework) in terms of how well the method can group (cluster) topologically similar networks. By testing this on both synthetic and real-world networks from different domains, we show that GCD remains the most accurate, noise-tolerant and computationally efficient alignment-free method. That is, we show that NetDis does not outperform the other methods, as originally claimed, while it is also computationally more expensive. Furthermore, since NetDis is dependent on the choice of a network null model (unlike the other graphlet-based methods), we show that its performance is highly sensitive to the choice of this parameter. Finally, we find that its performance is not independent on network sizes and densities, as originally claimed.

Contact: natasha@imperial.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
MeDuSa: a multi-draft based scaffolder
Authors: Bosi Emanuele , Donati Beatrice , Galardini Marco , Brunetti Sara , Sagot Marie-France , Lió Pietro , Crescenzi Pierluigi , Fani Renato , Fondi Marco
Published: March 2015

Motivation: Completing the genome sequence of an organism is an important task in comparative, functional and structural genomics. However, this remains a challenging issue from both a computational and an experimental viewpoint. Genome scaffolding (i.e. the process of ordering and orientating contigs) of de novo assemblies usually represents the first step in most genome finishing pipelines.

Results: In this article we present MeDuSa (Multi-Draft based Scaffolder), an algorithm for genome scaffolding. MeDuSa exploits information obtained from a set of (draft or closed) genomes from related organisms to determine the correct order and orientation of the contigs. MeDuSa formalizes the scaffolding problem by means of a combinatorial optimization formulation on graphs and implements an efficient constant factor approximation algorithm to solve it. In contrast to currently used scaffolders, it does not require either prior knowledge on the microrganisms dataset under analysis (e.g. their phylogenetic relationships) or the availability of paired end read libraries. This makes usability and running time two additional important features of our method. Moreover, benchmarks and tests on real bacterial datasets showed that MeDuSa is highly accurate and, in most cases, outperforms traditional scaffolders. The possibility to use MeDuSa on eukaryotic datasets has also been evaluated, leading to interesting results.

Availability and implementation: MeDuSa web server: http://combo.dbe.unifi.it/medusa. A stand-alone version of the software can be downloaded from https://github.com/combogenomics/medusa/releases. All results presented in this work have been obtained with MeDuSa v. 1.3.

Contact:  marco.fondi@unifi.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
H3K4 monomethylation dictates nucleosome dynamics and chromatin remodeling at stress-responsive genes
Authors: Nadal-Ribelles Mariona , Mas Glòria , Millán-Zambrano Gonzalo , Solé Carme , Ammerer Gustav , Chávez Sebastián , Posas Francesc , de Nadal Eulàlia
Published: March 2015

Chromatin remodeling is essential for proper adaptation to extracellular stimuli. The p38-related Hog1 SAPK is an important regulator of transcription that mediates chromatin remodeling upon stress. Hog1 targets the RSC chromatin remodeling complex to stress-responsive genes and rsc deficient cells display reduced induction of gene expression. Here we show that the absence of H3K4 methylation, either achieved by deletion of the SET1 methyltransferase or by amino acid substitution of H3K4, bypasses the requirement of RSC for stress-responsive gene expression. Monomethylation of H3K4 is specifically inhibiting RSC-independent chromatin remodeling and thus, it prevents osmostress-induced gene expression. The absence of H3K4 monomethylation permits that the association of alternative remodelers with stress-responsive genes and the Swr1 complex (SWR-C) is instrumental in the induction of gene expression upon stress. Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation. These results indicate that expression of stress-responsive genes is controlled by two remodeling mechanisms: RSC in the presence of monomethylated H3K4, and SWR-C in the absence of H3K4 monomethylation. Our findings point to a novel role for H3K4 monomethylation in dictating the specificity of chromatin remodeling, adding an extra layer of regulation to the transcriptional stress response.
Tibial Plateau Fracture Subluxation: An Effective Intraoperative Technique for the Reduction of Knee Joint Subluxation and Associated Medial Tibial Condyle Fragments
Authors: Sibai Tarek , Ricci William , Tornetta Paul
Published: March 2015

Knee subluxation or dislocation is an import associated component of many tibial plateau fracture patterns. Anatomic reduction of such tibial plateau fracture subluxation injuries requires reduction of both the associated fracture and the associated subluxation. Use of the femoral distractor in these situations will regain length, but holds the knee in relative fixed extension. A posterior approach increases the size of the incision and the dissection posteriorly while keeping the neurovascular structures on stretch. Described herein is an alternate technique to simply and effectively reduce tibial plateau fracture subluxations using periarticular clamps. Twenty-one patients with 1-year follow-up with successful outcomes have benefitted from this reduction technical tip thus far.
Improving Survival in Patients Treated for a Lung Cancer Using Self-Evaluated Symptoms Reported Through a Web Application
Authors: Denis Fabrice , Yossi Senna , Septans Anne-Lise , Charron Alexandre , Voog Eric , Dupuis Olivier , Ganem Gérard , Pointreau Yoann , Letellier Christophe
Published: March 2015

Objectives:

We retrospectively compared survivals in patients with a lung cancer history and followed by the so-called sentinel Web-application that allows early detection of relapse and early palliative care initiation versus a conventional follow-up in our center.

Methods:

The survival in 98 consecutive patients with lung cancer was assessed. The first part of them (the control arm) was retrospectively recruited between March 2011 and August 2012. The second half of them (the experimental arm) was prospectively recruited between August 2012 and December 2013 to weekly fill a form of 11 self-assessed symptoms, then processed by the “sentinel” Web-application. Data were sent to this sentinel application in real-time between planned visits. An email alert was sent to the oncologist when self-scored symptoms matched some predefined criteria. Follow-up visit and imaging were then organized after a phone call for confirming the suspect symptoms. In the control arm (49 patients), a common follow-up was applied (visit and imaging every 2 to 6 mo according to stage of tumor and kind of treatment).

Results:

Median follow-up duration was 12.3 months in the experimental arm and 16.7 months in the control arm (P=0.27). Survival was significantly better in the sentinel arm than in the control arm (P=0.0014). Median survival was 16.7 months in the control arm and 22.4 months in the experimental arm. One-year survival was 86.6% in the experimental arm and 59.1% in the control arm.

Conclusions:

Survival may be improved by early detection of relapse and early palliative care initiation by using sentinel-like Web-application.
Hierarchical analysis and multi-scale modelling of rat cortical and trabecular bone
Authors: Oftadeh Ramin , Entezari Vahid , Spörri Guy , Villa-Camacho Juan C. , Krigbaum Henry , Strawich Elsa , Graham Lila , Rey Christian , Chiu Hank , Müller Ralph , Hashemi Hamid Nayeb , Vaziri Ashkan , Nazarian Ara
Published: March 2015

The aim of this study was to explore the hierarchical arrangement of structural properties in cortical and trabecular bone and to determine a mathematical model that accurately predicts the tissue's mechanical properties as a function of these indices. By using a variety of analytical techniques, we were able to characterize the structural and compositional properties of cortical and trabecular bones, as well as to determine the suitable mathematical model to predict the tissue's mechanical properties using a continuum micromechanics approach. Our hierarchical analysis demonstrated that the differences between cortical and trabecular bone reside mainly at the micro- and ultrastructural levels. By gaining a better appreciation of the similarities and differences between the two bone types, we would be able to provide a better assessment and understanding of their individual roles, as well as their contribution to bone health overall.
A novel method for the purification of inositol phosphates from biological samples reveals that no phytate is present in human plasma or urine
Authors: Wilson Miranda S. C. , Bulley Simon J. , Pisani Francesca , Irvine Robin F. , Saiardi Adolfo
Published: March 2015

Inositol phosphates are a large and diverse family of signalling molecules. While genetic studies have discovered important functions for them, the biochemistry behind these roles is often not fully characterized. A key obstacle in inositol phosphate research in mammalian cells has been the lack of straightforward techniques for their purification and analysis. Here we describe the ability of titanium dioxide (TiO2) beads to bind inositol phosphates. This discovery allowed the development of a new purification protocol that, coupled with gel analysis, permitted easy identification and quantification of InsP6(phytate), its pyrophosphate derivatives InsP7and InsP8, and the nucleotides ATP and GTP from cell or tissue extracts. Using this approach, InsP6, InsP7and InsP8were visualized inDictyosteliumextracts and a variety of mammalian cell lines and tissues, and the effects of metabolic perturbation on these were explored. TiO2bead purification also enabled us to quantify InsP6in human plasma and urine, which led to two distinct but related observations. Firstly, there is an active InsP6phosphatase in human plasma, and secondly, InsP6is undetectable in either fluid. These observations seriously question reports that InsP6is present in human biofluids and the advisability of using InsP6as a dietary supplement.
Prognosis of anterior cruciate ligament reconstruction: a data-driven approach
Authors: Chandra Abhijit , Kar Oliva , Wu Kuan-Chuen , Hall Michelle , Gillette Jason
Published: March 2015

Individuals who suffer anterior cruciate ligament (ACL) injury are at higher risk of developing knee osteoarthritis (OA) and almost 50% display symptoms 10–20 years post injury.
Anterior cruciate ligament reconstruction
(
ACLR
)
often does not protect against knee OA development
. Accordingly, a multi-scale formulation for data-driven prognosis (DDP) of post-ACLR is developed. Unlike traditional predictive strategies that require controlled off-line measurements or ‘training’ for determination of constitutive parameters to derive the transitional statistics, the proposed DDP algorithm relies solely on
in situ
measurements. The proposed DDP scheme is capable of predicting onset of instabilities. As the need for off-line testing (or training) is obviated, it can be easily implemented for ACLR, where such controlled
a priori
testing is almost impossible to conduct. The DDP algorithm facilitates hierarchical handling of the large dataset and can assess the state of recovery in post-ACLR conditions based on data collected from stair ascent and descent exercises of subjects. The DDP algorithm identifies inefficient knee varus motion and knee rotation as primary difficulties experienced by some of the post-ACLR population. In such cases, levels of energy dissipation rate at the knee, and its fluctuation may be used as measures for assessing progress after ACL reconstruction.
Tatumella saanichensis sp. nov., isolated from a cystic fibrosis patient
Authors: Tracz Dobryan M. , Gilmour Matthew W. , Mabon Philip , Beniac Daniel R. , Hoang Linda , Kibsey Pamela , Van Domselaar Gary , Tabor Helen , Westmacott Garrett R. , Corbett Cindi R. , Bernard Kathryn A.
Published: March 2015

Polyphasic taxonomic analysis was performed on a clinical isolate (NML 06-3099T) from a cystic fibrosis patient, including whole-genome sequencing, proteomics, phenotypic testing, electron microscopy, chemotaxonomy and a clinical investigation. Comparative whole-genome sequence analysis and multilocus sequence analysis (MLSA) betweenTatumella ptyseosATCC 33301Tand clinical isolate NML 06-3099Tsuggested that the clinical isolate was closely related to, but distinct from, the speciesT. ptyseos. By 16S rRNA gene sequencing, the clinical isolate shared 98.7 % sequence identity withT. ptyseosATCC 33301T. A concatenate of six MLSA loci (totalling 4500 bp) revealed < 93.9 % identity betweenT. ptyseosATCC 33301T, other members of the genus and the clinical isolate. A whole-genome sequence comparison between NML 06-3099Tand ATCC 33301Tdetermined that the average nucleotide identity was 76.24 %. The overall DNA G+C content of NML 06-3099Twas 51.27 %, consistent with members of the genusTatumella. By matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis, NML 06-3099Thad a genus-level match, but not a species-level match, toT. ptyseos. By shotgun proteomics,T. ptyseosATCC 33301Tand NML 06-3099Twere found to have unique proteomes. The two strains had similar morphologies and multiple fimbriae, as observed by transmission electron microscopy, but were distinguishable by phenotypic testing. Cellular fatty acids found were typical for members of theEnterobacteriaceae. NML 06-3099Twas susceptible to commonly used antibiotics. Based on these data, NML 06-3099Trepresents a novel species in the genusTatumella, for which the nameTatumella saanichensissp. nov. is proposed (type strain NML 06-3099T = CCUG 55408T = DSM 19846T).