bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro development of preimplantation porcine embryos using alginate hydrogels as a three-dimensional extracellular matrix
Authors: Sargus-Patino Catherine N. , Wright Elane C. , Plautz Sarah A. , Miles Jeremy R. , Vallet Jeff L. , Pannier Angela K.
Published: August 2013

Between Days 10 and 12 of gestation, porcine embryos undergo a dramatic morphological change, known as elongation, with a corresponding increase in oestrogen production that triggers maternal recognition of pregnancy. Elongation deficiencies contribute to embryonic loss, but exact mechanisms of elongation are poorly understood due to the lack of an effective in vitro culture system. Our objective was to use alginate hydrogels as three-dimensional scaffolds that can mechanically support the in vitro development of preimplantation porcine embryos. White cross-bred gilts were bred at oestrus (Day 0) to Duroc boars and embryos were recovered on Days 9, 10 or 11 of gestation. Spherical embryos were randomly assigned to be encapsulated within double-layered 0.7% alginate beads or remain as non-encapsulated controls (ENC and CONT treatment groups, respectively) and were cultured for 96 h. Every 24 h, half the medium was replaced with fresh medium and an image of each embryo was recorded. At the termination of culture, embryo images were used to assess morphological changes and cell survival. 17β-Oestradiol levels were measured in the removed media by radioimmunoassay. Real-time polymerase chain reaction was used to analyse steroidogenic transcript expression at 96 h in ENC and CONT embryos, as well as in vivo-developed control embryos (i.e. spherical, ovoid and tubular). Although no differences in cell survival were observed, 32% (P < 0.001) of the surviving ENC embryos underwent morphological changes characterised by tubal formation with subsequent flattening, whereas none of the CONT embryos exhibited morphological changes. Expression of steroidogenic transcripts STAR, CYP11A1 and CYP19A1 was greater (P < 0.07) in ENC embryos with morphological changes (ENC+) compared with CONT embryos and ENC embryos with no morphological changes (ENC–), and was more similar to expression of later-stage in vivo-developed controls. Furthermore, a time-dependent increase (P < 0.001) in 17β-oestradiol was observed in culture media from ENC+ compared with ENC– and CONT embryos. These results illustrate that preimplantation pig embryos encapsulated in alginate hydrogels can undergo morphological changes with increased expression of steroidogenic transcripts and oestrogen production, consistent with in vivo-developed embryos. This alginate culture system can serve as a tool for evaluating specific mechanisms of embryo elongation that could be targeted to improve pregnancy outcomes.
Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions
Authors: Zeebe Richard E.
Published: August 2013

Climate sensitivity measures the response of Earth’s surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth’s climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO
2
solubility, which in turn leads to higher atmospheric CO
2
levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000–165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO
2
doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene–Eocene Thermal Maximum.
Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies
Authors: Sánchez-Martín David , Martínez-Torrecuadrada Jorge , Teesalu Tambet , Sugahara Kazuki N. , Alvarez-Cienfuegos Ana , Ximénez-Embún Pilar , Fernández-Periáñez Rodrigo , Martín M. Teresa , Molina-Privado Irene , Ruppen-Cañás Isabel , Blanco-Toribio Ana , Cañamero Marta , Cuesta Ángel M. , Compte Marta , Kremer Leonor , Bellas Carmen , Alonso-Camino Vanesa , Guijarro-Muñoz Irene , Sanz Laura , Ruoslahti Erkki , Alvarez-Vallina Luis
Published: August 2013

Antibody cancer therapies rely on systemically accessible targets and suitable antibodies that exert a functional activity or deliver a payload to the tumor site. Here, we present proof-of-principle of in vivo selection of human antibodies in tumor-bearing mice that identified a tumor-specific antibody able to deliver a payload and unveils the target antigen. By using an ex vivo enrichment process against freshly disaggregated tumors to purge the repertoire, in combination with in vivo biopanning at optimized phage circulation time, we have identified a human domain antibody capable of mediating selective localization of phage to human prostate cancer xenografts. Affinity chromatography followed by mass spectrometry analysis showed that the antibody recognizes the proteasome activator complex PA28. The specificity of soluble antibody was confirmed by demonstrating its binding to the active human PA28αβ complex. Whereas systemically administered control phage was confined in the lumen of blood vessels of both normal tissues and tumors, the selected phage spread from tumor vessels into the perivascular tumor parenchyma. In these areas, the selected phage partially colocalized with PA28 complex. Furthermore, we found that the expression of the α subunit of PA28 [proteasome activator complex subunit 1 (PSME1)] is elevated in primary and metastatic human prostate cancer and used anti-PSME1 antibodies to show that PSME1 is an accessible marker in mouse xenograft tumors. These results support the use of PA28 as a tumor marker and a potential target for therapeutic intervention in prostate cancer.
Forebrain dopamine neurons project down to a brainstem region controlling locomotion
Authors: Ryczko Dimitri , Grätsch Swantje , Auclair François , Dubé Catherine , Bergeron Saskia , Alpert Michael H. , Cone Jackson J. , Roitman Mitchell F. , Alford Simon , Dubuc Réjean
Published: August 2013

Significance

We found in lampreys that dopaminergic cells from the posterior tuberculum (homologue of the mammalian substantia nigra pars compacta and/or ventral tegmental area) not only send ascending projections to the striatum, but also have a direct descending projection to a brainstem region controlling locomotion—the mesencephalic locomotor region—where it releases dopamine (DA). DA increased locomotor output through a D1 receptor-dependent mechanism. The presence of this descending dopaminergic projection may have considerable implication for our understanding of the role of DA in motor control under physiological and pathological (i.e. Parkinson disease) conditions.
Population genomics reveals a possible history of backcrossing and recombination in the gynogenetic fish
Poecilia formosa
Authors: Alberici da Barbiano Laura , Gompert Zachariah , Aspbury Andrea S. , Gabor Caitlin R. , Nice Chris C.
Published: August 2013

Unisexual sperm-dependent vertebrates are of hybrid origins, rare, and predicted to be short-lived as a result of several challenges arising from their mode of reproduction. In particular, because of a lack of recombination, clonal species are predicted to have a low potential to respond to natural selection. However, many unisexual sperm-dependent species persist, and assessing the genetic diversity present in these species is fundamental to understanding how they avoid extinction. We used population genomic methods to assess genotypic variation within the unisexual fish
Poecilia formosa
. Measures of admixture and population differentiation, as well as clustering analyses, indicate that the genomes of individuals of
P. formosa
are admixed and intermediate between
Poecilia latipinna
and
Poecilia mexicana
, consistent with the hypothesis of their hybrid origins. Bayesian genomic cline analyses indicate that about 12% of sampled loci exhibit patterns consistent with inheritance from only one parent. The estimation of observed heterozygosity clearly suggests that
P. formosa
is not comprised of direct descendants of a single nonrecombining asexual F
1
hybrid individual. Additionally, the estimation of observed heterozygosity provides support for the hypothesis that the history of this unisexual species has included backcrossing with the parent species before the onset of gynogenesis. We also document high levels of variation among asexual individuals, which is attributable to recombination (historical or ongoing) and the accumulation of mutations. The high genetic variation suggests that this unisexual vertebrate has more potential to respond to natural selection than if they were frozen F
1
hybrids.
Unifying model for molecular determinants of the preselection Vβ repertoire
Authors: Gopalakrishnan Suhasni , Majumder Kinjal , Predeus Alexander , Huang Yue , Koues Olivia I. , Verma-Gaur Jiyoti , Loguercio Salvatore , Su Andrew I. , Feeney Ann J. , Artyomov Maxim N. , Oltz Eugene M.
Published: August 2013

Significance

The assembly of immunoglobulin and T-cell receptor genes by V(D)J (variable, diversity, joining) recombination must strike a balance between maximum diversification of antigen receptors and favoring gene segments with specialized functions. We quantified the use of V gene segments in the primary T-cell receptor β repertoire, defining the relative contribution of 13 parameters in shaping their recombination efficiencies. Computational analysis of these data provides a unifying model, revealing a minimal set of five parameters that predict Vβ use. This model building approach will help predict how natural alterations of large V clusters impact immune receptor repertoires.
Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2
Authors: Furness David N. , Johnson Stuart L. , Manor Uri , Rüttiger Lukas , Tocchetti Arianna , Offenhauser Nina , Olt Jennifer , Goodyear Richard J. , Vijayakumar Sarath , Dai Yuhai , Hackney Carole M. , Franz Christoph , Di Fiore Pier Paolo , Masetto Sergio , Jones Sherri M. , Knipper Marlies , Holley Matthew C. , Richardson Guy P. , Kachar Bechara , Marcotti Walter
Published: August 2013

Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during development and in the adult. We show that the actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, a member of the Eps8-like protein family, is a newly identified hair bundle protein that is localized at the tips of stereocilia of both cochlear and vestibular hair cells. It has a spatiotemporal expression pattern that complements that of Eps8. In the cochlea, whereas Eps8 is essential for the initial elongation of stereocilia, Eps8L2 is required for their maintenance in adult hair cells. In the absence of both proteins, the ordered staircase structure of the hair bundle in the cochlea decays. In contrast to the early profound hearing loss associated with an absence of Eps8, Eps8L2 null-mutant mice exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology. We conclude that Eps8L2 is required for the long-term maintenance of the staircase structure and mechanosensory function of auditory hair bundles. It complements the developmental role of Eps8 and is a candidate gene for progressive age-related hearing loss.
Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network
Authors: Motta Simone C. , Guimarães Cibele Carla , Furigo Isadora Clivatti , Sukikara Marcia Harumi , Baldo Marcus V. C. , Lonstein Joseph S. , Canteras Newton S.
Published: August 2013

Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomic responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression.
Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice
Authors: Imai Yasutomo , Yasuda Koubun , Sakaguchi Yoshiko , Haneda Takashi , Mizutani Hitoshi , Yoshimoto Tomohiro , Nakanishi Kenji , Yamanishi Kiyofumi
Published: August 2013

Transgenic mice expressing the mouse interleukin 33 (IL-33) gene driven by a keratin 14 promoter were generated. The skin-selective expression of the IL-33 gene was enhanced, and intense immunofluorescence for IL-33 was evident in the nuclei of the epidermis. Spontaneous itchy dermatitis developed in those mice at 6–8 wk of age in specific pathogen-free conditions. In the lesional skin, the epidermis was thickened and the eosinophils were infiltrated with increased expression of the eosinophil peroxidase and major basic protein genes. Mast cells were also abundant there, and blood histamine and total IgE levels were high. Those phenotypes closely resemble the features of atopic dermatitis. In peripheral blood and lesional skin, IL-5, IL-13, regulated upon activation, normally T-expressed, and presumably secreted (RANTES)/CCL5, and Eotaxin 1/CCL11 were increased, whereas TNF-α, IFN-γ, and thymic stromal lymphopoietin (TSLP) were unaltered. Furthermore, the proportion of group 2 innate lymphoid cells (ILC2s), which produce IL-5, were significantly increased in the lesional skin, peripheral blood, and regional lymph nodes. The dermatitis with eosinophil infiltration was improved by the administration of an anti-IL-5 antibody. These results suggest that the expression of IL-33 in the skin activates an immune response involving ILC2 and that this process might play a crucial role in the pathogenesis of allergic inflammation that is characteristic of atopic dermatitis.
Newborn chickens generate invariant object representations at the onset of visual object experience
Authors: Wood Justin N.
Published: August 2013

To recognize objects quickly and accurately, mature visual systems build invariant object representations that generalize across a range of novel viewing conditions (e.g., changes in viewpoint). To date, however, the origins of this core cognitive ability have not yet been established. To examine how invariant object recognition develops in a newborn visual system, I raised chickens from birth for 2 weeks within controlled-rearing chambers. These chambers provided complete control over all visual object experiences. In the first week of life, subjects’ visual object experience was limited to a single virtual object rotating through a 60° viewpoint range. In the second week of life, I examined whether subjects could recognize that virtual object from novel viewpoints. Newborn chickens were able to generate viewpoint-invariant representations that supported object recognition across large, novel, and complex changes in the object’s appearance. Thus, newborn visual systems can begin building invariant object representations at the onset of visual object experience. These abstract representations can be generated from sparse data, in this case from a visual world containing a single virtual object seen from a limited range of viewpoints. This study shows that powerful, robust, and invariant object recognition machinery is an inherent feature of the newborn brain.
Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system
Authors: Jao Li-En , Wente Susan R. , Chen Wenbiao
Published: August 2013

A simple and robust method for targeted mutagenesis in zebrafish has long been sought. Previous methods generate monoallelic mutations in the germ line of F0 animals, usually delaying homozygosity for the mutation to the F2 generation. Generation of robust biallelic mutations in the F0 would allow for phenotypic analysis directly in injected animals. Recently the type II prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system has been adapted to serve as a targeted genome mutagenesis tool. Here we report an improved CRISPR/Cas system in zebrafish with custom guide RNAs and a zebrafish codon-optimized Cas9 protein that efficiently targeted a reporter transgene
Tg(-5.1mnx1:egfp)
and four endogenous loci (
tyr
,
golden
,
mitfa
, and
ddx19
). Mutagenesis rates reached 75–99%, indicating that most cells contained biallelic mutations. Recessive null-like phenotypes were observed in four of the five targeting cases, supporting high rates of biallelic gene disruption. We also observed efficient germ-line transmission of the Cas9-induced mutations. Finally, five genomic loci can be targeted simultaneously, resulting in multiple loss-of-function phenotypes in the same injected fish. This CRISPR/Cas9 system represents a highly effective and scalable gene knockout method in zebrafish and has the potential for applications in other model organisms.
Prevalent mechanism of membrane bridging by synaptotagmin-1
Authors: Seven Alpay B. , Brewer Kyle D. , Shi Liang , Jiang Qiu-Xing , Rizo Josep
Published: August 2013

Significance

The ability of synaptotagmin-1 to bridge two membranes is likely critical for its function as a Ca
2+
sensor in neurotransmitter release. A synaptotagmin-1 fragment spanning its two C
2
domains bridges membranes directly, binding simultaneously to both membranes. However, a longer synaptotagmin-1 fragment spanning most of its cytoplasmic region was proposed to bridge membranes through protein–protein interactions between oligomers bound to each membrane. This paper now shows that direct bridging actually constitutes the prevalent mechanism of membrane bridging by the longer synaptotagmin-1 fragment. These findings strongly suggest that direct membrane bridging underlies the function of synaptotagmin-1 in neurotransmitter release.
Comparative studies of Munc18c and Munc18-1 reveal conserved and divergent mechanisms of Sec1/Munc18 proteins
Authors: Yu Haijia , Rathore Shailendra S. , Lopez Jamie A. , Davis Eric M. , James David E. , Martin Jennifer L. , Shen Jingshi
Published: August 2013

Significance

Sec1/Munc18 (SM) proteins are essential for every vesicle fusion pathway, but their molecular mechanisms remain poorly understood. Our comparative studies of two functionally distinct SM proteins, Munc18c and Munc18-1, suggest that one conserved function of SM proteins is to recognize their cognatetrans-SNARE complexes and accelerate fusion kinetics. The “closed” syntaxin binding mode of Munc18-1, however, is not conserved in Munc18c. Unexpectedly, we discovered that the architecture of the SNARE/SM complex differs across fusion pathways. Together, these findings reveal conserved as well as divergent functions of SM proteins in vesicle fusion.
Enabling enhanced emission and low-threshold lasing of organic molecules using special Fano resonances of macroscopic photonic crystals
Authors: Zhen Bo , Chua Song-Liang , Lee Jeongwon , Rodriguez Alejandro W. , Liang Xiangdong , Johnson Steven G. , Joannopoulos John D. , Soljačić Marin , Shapira Ofer
Published: August 2013

The nature of light interaction with matter can be dramatically altered in optical cavities, often inducing nonclassical behavior. In solid-state systems, excitons need to be spatially incorporated within nanostructured cavities to achieve such behavior. Although fascinating phenomena have been observed with inorganic nanostructures, the incorporation of organic molecules into the typically inorganic cavity is more challenging. Here, we present a unique optofluidic platform comprising organic molecules in solution suspended on a photonic crystal surface, which supports macroscopic Fano resonances and allows strong and tunable interactions with the molecules anywhere along the surface. We develop a theoretical framework of this system and present a rigorous comparison with experimental measurements, showing dramatic spectral and angular enhancement of emission. We then demonstrate that these enhancement mechanisms enable lasing of only a 100-nm thin layer of diluted solution of organic molecules with substantially reduced threshold intensity, which has important implications for organic light-emitting devices and molecular sensing.
Brief meditation training induces smoking reduction
Authors: Tang Yi-Yuan , Tang Rongxiang , Posner Michael I.
Published: August 2013

More than 5 million deaths a year are attributable to tobacco smoking, but attempts to help people either quit or reduce their smoking often fail, perhaps in part because the intention to quit activates brain networks related to craving. We recruited participants interested in general stress reduction and randomly assigned them to meditation training or a relaxation training control. Among smokers, 2 wk of meditation training (5 h in total) produced a significant reduction in smoking of 60%; no reduction was found in the relaxation control. Resting-state brain scans showed increased activity for the meditation group in the anterior cingulate and prefrontal cortex, brain areas related to self-control. These results suggest that brief meditation training improves self-control capacity and reduces smoking.
Argument kinds and argument roles in the Ontario provincial election, 2011
Authors: Hansen Hans V. , Walton Douglas N.
Published: August 2013

This paper is a report of a pilot study of how candidates argue when they are running for political office. The election studied was the provincial election in Ontario, Canada, in the fall of 2011. Having collected about 250 arguments given during the election from newspaper media, we sought answers to the following questions, among others: (i) which argumentation schemes have the greatest currency in political elections? (ii) Is a list of the best known argumentation schemes sufficient to classify the arguments given in elections? (iii) What schemes should be added to the familiar list to make it more adequate for studying elections? (iv) Is it useful to classify arguments as being used for positive, policy-critical, person-critical and defensive purposes? (v) Can political parties be usefully characterized by noting their preferred kinds of arguments and their most frequent uses of arguments? (vi) What lessons can be learned from this study to better design future studies of the same kind?
Field and Laboratory Evaluation of Dam Escapement of Muskellunge
Authors: Wolter Max H. , DeBoom Corey S. , Wahl David H.
Published: August 2013

Muskellunge Esox masquinongy occur in many Midwestern reservoirs where dam escapement is often reported. Because densities of Muskellunge in many reservoirs are low, escapement is a concern. Little is known regarding the factors that influence rates of Muskellunge dam escapement or the proportion of reservoir populations that escape annually. We used controlled laboratory experiments to examine how juvenile Muskellunge interact with flow over a barrier at varying levels of turbidity, flow rate, habitat availability, and periods in the diel cycle. In the field we inserted PIT tags into juvenile and adult Muskellunge, monitored their escapement over a dam with an antenna array, and then compared escapement among demographic groups and described escapement in relation to precipitation events, water temperature, and water clarity. Both laboratory and field studies found Muskellunge were more likely to escape during the day than at night. We estimated that 25% of a reservoir Muskellunge population escaped within the 1-year period of this study, with escapement occurring during late spring but not during fall. Adults were more likely to escape than juveniles, and both sexes escaped at equal rates. Methods developed here can be used to provide useful information to managers and develop mitigation practices to limit escapement in situations where it is not desirable.

Received March 19, 2013; accepted June 3, 2013
Sexual Dimorphism in Alligator Gar
Authors: McDonald D. L. , Anderson J. D. , Hurley C. , Bumguardner B. W. , Robertson C. R.
Published: August 2013

The Alligator Gar Atractosteus spatula is currently imperiled due to habitat alterations and overharvest within much of this species’ range. Recent interest in improving management for this species within the USA and Mexico has spurred new creel restrictions, spawning area closures, and stocking programs, along with increased research on life history and population dynamics. These management and research measures can be improved by a noninvasive method for determining sex. Previous methods have required sacrificing the fish (for internal anatomy confirmation) or using costly and time-consuming assays from a specialized laboratory. Evidence from other gar species suggests that sex determination is possible by examining sexually dimorphic external characters. We evaluated the utility of 13 morphological measurements for determining the sex of Alligator Gars of known gender (n = 117; SL range, 591–1,255 mm). Discriminate analysis identified two influential variables (snout length and caudal peduncle height) as sexually dimorphic. Univariate analyses identified three variables as sexually dimorphic (head length, snout length, and anal fin base length). Sexually dimorphic variables were used with SL to develop a method using serial body ratios (SL/snout length) followed by (snout length/anal fin base length) to identify sex in Alligator Gar to 93% accuracy in males and 72% accuracy in females.

Received April 1, 2013; accepted June 3, 2013
Effects of Salmon Gonadotropin-Releasing Hormone Analog (GnRHa) on Reproductive Success and Egg Size in Rainbow Trout and Brook Trout
Authors: Svinger Viktor W , Policar Tomáš , Kallert Dennis M , Kouřil Jan
Published: August 2013

Rainbow Trout Oncorhynchus mykiss were treated with a 100- or 25-μg/kg dose of salmon gonadotropin-releasing hormone analog (sGnRHa) that was emulsified in Freund's incomplete adjuvant (FIA). Controls were treated with a mixture of FIA and physiological saline. Latency (number of days from the first injection to the date of detected ovulation) was significantly shortened in treated groups compared with the control group. Egg weight, eyeing rate, and hatching rate were significantly reduced in treated groups; mortality after the eyed stage was significantly higher in treated groups. The relationship between latency and the eyeing rate or hatching rate was positive, but the relationship between latency and mortality after the eyed stage was negative. Brook Trout Salvelinus fontinalis were treated with a single injection of sGnRHa–FIA at 12.5 μg/kg, double acute injections of sGnRHa at 12.5 μg/kg administered 3 d apart, or a single acute injection of sGnRHa at 50 μg/kg. Controls were injected with FIA and physiological saline. Latency was significantly shortened in treated groups except the group that received the single acute injection of 50 μg/kg. Egg weight and alevin weight were significantly lower in treated groups. Egg mortality after the eyed stage was significantly higher in the double-injected group than in the 12.5-μg/kg sGnRHa–FIA group and the control group. Latency had a negative relationship with the eyeing rate and hatching rate. This result for Brook Trout is opposite that observed for Rainbow Trout. Latency and mortality after the eyed stage were not correlated. It is evident that the experimental designs currently used in salmonid research should be updated to determine reliable means of avoiding egg mortality, particularly in Rainbow Trout, after GnRHa treatment.
The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2
Authors: Zou Weiguo , Greenblatt Matthew B. , Brady Nicholas , Lotinun Sutada , Zhai Bo , de Rivera Heather , Singh Anju , Sun Jun , Gygi Steven P. , Baron Roland , Glimcher Laurie H. , Jones Dallas C.
Published: August 2013

Osteoblasts are responsible for the formation and mineralization of the skeleton. To identify novel regulators of osteoblast differentiation, we conducted an unbiased forward genetic screen using a lentiviral-based shRNA library. This functional genomics analysis led to the identification of the microtubule-associated protein DCAMKL1 (Doublecortin-like and CAM kinase–like 1) as a novel regulator of osteogenesis. Mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts. Molecular experiments demonstrated that DCAMKL1 represses osteoblast activation by antagonizing Runx2, the master transcription factor in osteoblasts. Key elements of the cleidocranial dysplasia phenotype observed in Runx2+/− mice are reversed by the introduction of a Dcamkl1-null allele. Our results establish a genetic linkage between these two proteins in vivo and demonstrate that DCAMKL1 is a physiologically relevant regulator of anabolic bone formation.
Stronger Lasota-Yorke inequality for one-dimensional piecewise expanding transformations
Authors: Eslami Peyman , Góra Pawel
Published: August 2013

For a large class of piecewise expanding

C

1
,
1

\mathcal {C}^{1,1}

maps of the interval we prove the Lasota-Yorke inequality with a constant smaller than the previously known

2

/

inf

|

τ
′

|

2/\inf |\tau ’|

. Consequently, the stability results of Keller-Liverani apply to this class and in particular to maps with periodic turning points. One of the applications is the stability of acim’s for a class of W-shaped maps. Another application is an affirmative answer to a conjecture of Eslami-Misiurewicz regarding acim-stability of a family of unimodal maps.
Positive solutions for vector differential equations
Authors: Wang Yan
Published: August 2013

In this paper, we are concerned with the existence and multiplicity of positive periodic solutions for first-order vector differential equations. By using the Leray-Schauder alternative theorem and the Kransnosel’skii fixed point theorem, we show that the differential equations under the periodic boundary value conditions have at least two positive periodic solutions.
Twisted Kodaira-Spencer classes and the geometry of surfaces of general type
Authors: Naie Daniel , Reider Igor
Published: August 2013

We study the cohomology groups

H
1

(
X
,

Θ
X

(
−
m

K
X

)
)

H^1(X,\Theta _X(-mK_X))

, for

m
≥
1

m\geq 1

, where

X
X

is a smooth minimal complex surface of general type,

Θ
X

\Theta _X

its holomorphic tangent bundle, and

K
X

K_X

its canonical divisor. One of the main results is a precise vanishing criterion for

H
1

(
X
,

Θ
X

(
−

K
X

)
)

H^1(X,\Theta _X (-K_X))

(Theorem 1.1).

The proof is based on the geometric interpretation of non-zero cohomology classes of

H
1

(
X
,

Θ
X

(
−

K
X

)
)

H^1(X,\Theta _X (-K_X))

. This interpretation in turn uses higher rank vector bundles on

X
X

.

We apply our methods to the long standing conjecture saying that the irregularity of surfaces in

P

4

\mathbb {P}^4

is at most

2
2

. We show that if

X
X

has bounded holomorphic Euler characteristic, no irrational pencil, and is embedded in

P

4

\mathbb {P}^4

with a sufficiently large degree, then the irregularity of

X
X

is at most

3
3

.
Would you be a geriatrician? Student career preferences and attitudes to a career in geriatric medicine
Authors: Ní Chróinín Danielle , Cronin Edel , Cullen Walter , O'Shea Diarmuid , Steele Michael , Bury Gerard , Kyne Lorraine
Published: August 2013

Background: career intentions of medical students may impact on education and workforce planning. We sought to determine (i) career choices of senior medical students; (ii) interest in geriatric medicine; (iii) factors influencing such choices; and (iv) the impact of a 6-week Medicine in the Community module.

Methods: cross-sectional survey of all senior UCD medical students, before and after completion of a ‘Medicine in the Community’ module, 2009–11.

Results: eighty-two per cent (274/336) completed the survey at module's end. Two-thirds (174) had chosen a future speciality, most frequently general practice (32.1%) and internal medicine (17%). Half (49.8%) believed career selection is made during medical school. Thirty-one per cent would consider a career in geriatric medicine; reasons cited were interesting field (34.5%), clinical variety (25%) and perception as emotionally rewarding (20.2%). Commonest deterrents were perceived slowness-of-pace and not wanting to work with older patients. Female students (adjusted OR: 1.89, P = 0.05) and those prioritising travel opportunities (adjusted OR: 2.77, P = 0.01) were more likely to consider geriatric medicine. Half (51.5%) reported that the community medicine module increased their interest in geriatric medicine; 91.3% that it would positively influence how they treated older patients. Students reporting a positive influence of the module were more likely to consider a career in geriatric medicine (OR: 1.62, P = 0.02).

Conclusion: two-thirds of students had already chosen a future speciality. One-third would consider geriatric medicine. This may have important implications for workforce planning and development of geriatric medicine. Undergraduate exposure to the discipline may increase interest in geriatric medicine as a career, and positively influence management of older patients.
Impact of Cost Shocks on Consumer Prices in Vertically‐Related Markets: The Case of The French Soft Drink Market
Authors: Bonnet Céline , Réquillart Vincent
Published: August 2013

We develop a structural econometric model of the vertical contracts between soft drink manufacturers and retailers to assess the impact of taxes or changes in production costs on consumer prices. Using individual data on food purchases from a representative survey of 19,000 French households in 2005, we estimate consumer demand using a random utility approach. Among a set of possible vertical relationships, we select the model that best fits the data. We evaluate the pass‐through rate of changes in input costs (sugar) or of taxes and show that the industry over‐shifts cost changes or excise taxes to the consumers. This result challenges the belief that firms do not pass on the full extent of cost changes or excise taxes to consumers.
Distilled single-cell genome sequencing and de novo assembly for sparse microbial communities
Authors: Taghavi Zeinab , Movahedi Narjes S. , Drǎghici Sorin , Chitsaz Hamidreza
Published: August 2013

Motivation: Identification of every single genome present in a microbial sample is an important and challenging task with crucial applications. It is challenging because there are typically millions of cells in a microbial sample, the vast majority of which elude cultivation. The most accurate method to date is exhaustive single-cell sequencing using multiple displacement amplification, which is simply intractable for a large number of cells. However, there is hope for breaking this barrier, as the number of different cell types with distinct genome sequences is usually much smaller than the number of cells.

Results: Here, we present a novel divide and conquer method to sequence and de novo assemble all distinct genomes present in a microbial sample with a sequencing cost and computational complexity proportional to the number of genome types, rather than the number of cells. The method is implemented in a tool called Squeezambler. We evaluated Squeezambler on simulated data. The proposed divide and conquer method successfully reduces the cost of sequencing in comparison with the naïve exhaustive approach.

Availability: Squeezambler and datasets are available at http://compbio.cs.wayne.edu/software/squeezambler/.

Contact:  ztaghavi@wayne.edu
CellMissy: a tool for management, storage and analysis of cell migration data produced in wound healing-like assays
Authors: Masuzzo Paola , Hulstaert Niels , Huyck Lynn , Ampe Christophe , Van Troys Marleen , Martens Lennart
Published: August 2013

Summary: Automated image processing has allowed cell migration research to evolve to a high-throughput research field. As a consequence, there is now an unmet need for data management in this domain. The absence of a generic management system for the quantitative data generated in cell migration assays results in each dataset being treated in isolation, making data comparison across experiments difficult. Moreover, by integrating quality control and analysis capabilities into such a data management system, the common practice of having to manually transfer data across different downstream analysis tools will be markedly sped up and made more robust. In addition, access to a data management solution creates gateways for data standardization, meta-analysis and structured public data dissemination.

We here present CellMissy, a cross-platform data management system for cell migration data with a focus on wound healing data. CellMissy simplifies and automates data management, storage and analysis from the initial experimental set-up to data exploration.

Availability and implementation: CellMissy is a cross-platform open-source software developed in Java. Source code and cross-platform binaries are freely available under the Apache2 open source license at http://cellmissy.googlecode.com.

Contact:  lennart.martens@ugent.be

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Scaffold network generator: a tool for mining molecular structures
Authors: Matlock Matt K. , Zaretzki Jed M. , Swamidass S. Joshua
Published: August 2013

Summary: Scaffold network generator (SNG) is an open-source command-line utility that computes the hierarchical network of scaffolds that define a large set of input molecules. Scaffold networks are useful for visualizing, analysing and understanding the chemical data that is increasingly available through large public repositories like PubChem. For example, some groups have used scaffold networks to identify missed-actives in high-throughput screens of small molecules with bioassays. Substantially improving on existing software, SNG is robust enough to work on millions of molecules at a time with a simple command-line interface.

Availability and implementation: SNG is accessible at http://swami.wustl.edu/sng

Contact:  swamidass@wustl.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A distance-based test of association between paired heterogeneous genomic data
Authors: Minas Christopher , Curry Edward , Montana Giovanni
Published: August 2013

Motivation: Due to rapid technological advances, a wide range of different measurements can be obtained from a given biological sample including single nucleotide polymorphisms, copy number variation, gene expression levels, DNA methylation and proteomic profiles. Each of these distinct measurements provides the means to characterize a certain aspect of biological diversity, and a fundamental problem of broad interest concerns the discovery of shared patterns of variation across different data types. Such data types are heterogeneous in the sense that they represent measurements taken at different scales or represented by different data structures.

Results: We propose a distance-based statistical test, the generalized RV (GRV) test, to assess whether there is a common and non-random pattern of variability between paired biological measurements obtained from the same random sample. The measurements enter the test through the use of two distance measures, which can be chosen to capture a particular aspect of the data. An approximate null distribution is proposed to compute P-values in closed-form and without the need to perform costly Monte Carlo permutation procedures. Compared with the classical Mantel test for association between distance matrices, the GRV test has been found to be more powerful in a number of simulation settings. We also demonstrate how the GRV test can be used to detect biological pathways in which genetic variability is associated to variation in gene expression levels in an ovarian cancer sample, and present results obtained from two independent cohorts.

Availability: R code to compute the GRV test is freely available from http://www2.imperial.ac.uk/∼gmontana

Contact: g.montana@imperial.ac.uk

Supplementary data: Supplementary data are available at Bioinformatics online.
The BioPAX Validator
Authors: Rodchenkov Igor , Demir Emek , Sander Chris , Bader Gary D.
Published: August 2013

Summary: BioPAX is a community-developed standard language for biological pathway data. A key functionality required for efficient BioPAX data exchange is validation—detecting errors and inconsistencies in BioPAX documents. The BioPAX Validator is a command-line tool, Java library and online web service for BioPAX that performs >100 classes of consistency checks.

Availability and implementation: The validator recognizes common syntactic errors and semantic inconsistencies and reports them in a customizable human readable format. It can also automatically fix some errors and normalize BioPAX data. Since its release, the validator has become a critical tool for the pathway informatics community, detecting thousands of errors and helping substantially increase the conformity and uniformity of BioPAX-formatted data. The BioPAX Validator is open source and released under LGPL v3 license. All sources, binaries and documentation can be found at sf.net/p/biopax, and the latest stable version of the web application is available at biopax.org/validator.

Contact:  igor.rodchenkov@utoronto.ca or gary.bader@utoronto.ca
HD in C
60
: theoretical prediction of the inelastic neutron scattering spectrum and its temperature dependence
Authors: Xu Minzhong , Ye Shufeng , Lawler Ronald , Turro Nicholas J. , Bačić Zlatko
Published: August 2013

We report rigorous quantum calculations of the inelastic neutron scattering (INS) spectra of HD@C
60
, over a range of temperatures from 0 to 240 K and for two incident neutron wavelengths used in recent experimental investigations. The computations were performed using our newly developed methodology, which incorporates the coupled five-dimensional translation–rotation (T–R) eigenstates of the guest molecule as the initial and final states of the INS transitions, and yields highly detailed spectra. Depending on the incident neutron wavelength, the number of computed INS transitions varies from almost 500 to over 2000. The low-temperature INS spectra display the fingerprints of the coupling between the translational and rotational motions of the entrapped HD molecule, which is responsible for the characteristic splitting patterns of the T–R energy levels. INS transitions from the ground T–R state of HD to certain sublevels of excited T–R multiplets have zero intensity and are absent from the spectra. This surprising finding is explained by the new INS selection rule introduced here. The calculated spectra exhibit strong temperature dependence. As the temperature increases, numerous new peaks appear, arising from the transitions originating in excited T–R states which become populated. Our calculations show that the higher temperature features typically comprise two or more transitions close in energy and with similar intensities, interspersed with numerous other transitions whose intensities are negligible. This implies that accurately calculated energies and intensities of INS transitions which our methodology provides will be indispensable for reliable interpretation and assignment of the experimental spectra of HD@C
60
and related systems at higher temperatures.
Probing the C
60
triplet state coupling to nuclear spins inside and out
Authors: Filidou Vasileia , Mamone Salvatore , Simmons Stephanie , Karlen Steven D. , Anderson Harry L. , Kay Christopher W. M. , Bagno Alessandro , Rastrelli Federico , Murata Yasujiro , Komatsu Koichi , Lei Xuegong , Li Yongjun , Turro Nicholas J. , Levitt Malcolm H. , Morton John J. L.
Published: August 2013

The photoexcitation of functionalized fullerenes to their paramagnetic triplet electronic state can be studied by pulsed electron paramagnetic resonance (EPR) spectroscopy, whereas the interactions of this state with the surrounding nuclear spins can be observed by a related technique: electron nuclear double resonance (ENDOR). In this study, we present EPR and ENDOR studies on a functionalized exohedral fullerene system, dimethyl[9-hydro (C60-Ih)[5,6]fulleren-1(9
H
)-yl]phosphonate (DMHFP), where the triplet electron spin has been used to hyperpolarize, couple and measure two nuclear spins. We go on to discuss the extension of these methods to study a new class of endohedral fullerenes filled with small molecules, such as H
2
@C
60
, and we relate the results to density functional calculations.
Nanolaboratories: physics and chemistry of small-molecule endofullerenes
Authors: Levitt Malcolm H. , Horsewill Anthony J.
Published: August 2013

This Theo Murphy Meeting Issue contains papers presented at a Discussion Meeting held at the Kavli Centre of the Royal Society in March 2012. The meeting brought together a wide variety of scientists working on different aspects of small-molecule endofullerenes—those intriguing chemical systems in which small molecules such as H
2
or H
2
O are encapsulated in tiny carbon cages.