bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of post-weaning mortality of sheep in Australia and its association with farm and management factors
Authors: Campbell Angus J. D. , Broekhuizen Annefleur , Curtis Kimbal , Croker Keith P. , Behrendt Ralph , Thompson Andrew N.
Published: September 2013

A cross-sectional telephone survey of post-weaning sheep management and mortality was conducted involving 1410 farmers from across Australia. The average reported post-weaning mortality was 4.6%. Mortality was greatest in Queensland and Western Australia, and least in New South Wales, Victoria, and South Australia. Weaner mortality was also greater in the pastoral zone than in the sheep–cereals or high-rainfall zones. Overall, 44% of farms had mortality identified as ‘high’, exceeding the suggested benchmark of ≤4% per annum. High mortality was reported on 50% and 32% of farms with predominantly Merino and crossbred weaners, respectively. There was no statistically significant association between high mortality and the main month of lambing for a flock. Larger sheep flocks, flocks with a smaller proportion of weaners, and farms of smaller area were associated with a greater likelihood of high weaner mortality. The odds of high mortality in weaner flocks that were routinely separated according to bodyweight or condition score was half that of flocks that were managed as one group. Overall, 84% of farmers regularly provided supplementary feed to weaner sheep, but the kind of supplement offered and the proportions of farms routinely supplementing differed between states and sheep production zones. Only high-protein supplementary feeding was associated with lower odds of high mortality. This survey confirms that poor post-weaning survival remains a widespread issue for the Australian sheep industry but identifies farm and management factors associated with reduced weaner mortality.
The effect of sodicity on cotton: Does soil chemistry or soil physical condition have the greater role?
Authors: Dodd K. , Guppy C. N. , Lockwood P. V. , Rochester I. J.
Published: September 2013

Soil sodicity is widespread in the cracking clays used for irrigated cotton (Gossypium hirsutum L.) production in Australia and worldwide and sometimes produces nutrient imbalances and poor plant growth. It is not known whether these problems are due primarily to soil physical or to soil chemical constraints. We investigated this question by growing cotton to maturity in a glasshouse in large samples of a Grey Vertosol in which the exchangeable sodium percentage (ESP) was adjusted to 2, 13, 19, or 24. A soil-stabilising agent, anionic polyacrylamide (PAM), was added to half the pots and stabilised soil aggregation at all ESPs. Comparison of the effect of ESP on cotton in the pots with and without PAM showed that, up to ESP of 19, the soil physical effects of sodicity were mainly responsible for poor cotton performance and its ability to accumulate potassium. At ESP >19, PAM amendment did not significantly improve lint yield, indicating that soil chemical constraints, high plant sodium concentrations (>0.2%), and marginal plant manganese concentrations limited plant performance. Further research into commercial methods of amelioration of poor physical condition is warranted rather than application of more fertiliser.
Pastoralists’ knowledge of plant palatability and grazing indicators in an arid region of South Australia
Authors: Waudby Helen P. , Petit Sophie , Robinson Guy
Published: September 2013

Indicator species have been used for several decades as measures of ecosystem health. In arid Australian rangelands, which are dominated by commercial grazing enterprises reliant on native pastures, the development of efficacious indicators is particularly important to monitor production and biodiversity values. The high temporal and spatial climatic variability of arid rangelands means that developing broad indicators is difficult and resource intensive. However, pastoralists, who observe their pastures and the species favoured by stock under a range of conditions, can provide information on local indicators. This paper examines pastoralists’ knowledge in terms of its value for natural resource management in rangelands, including their use of local indicators and understanding of palatability of selected plant species. A survey was mailed to all 51 occupants of pastoral properties in the Stony Plains region of South Australia. Pastoralists were asked what species they considered indicators of overgrazing, whether they would destock if they noted changes in these indicators, what they knew of the palatability of certain plant species, and the usefulness of cracking-clay areas (a key landscape feature in the region) for grazing. Views of respondents on indicator species and plant palatability mostly concurred with published reports on the preferences of livestock for these species. A wide range of indicators (all perennial plant species and no animal species) was listed by respondents, suggesting that indicators are highly location-specific, plant-focussed, and not viewed consistently among pastoralists. Respondents related specific information about cracking-clay areas on their leases, including the influence of the timing and amount of rainfall on pasture productivity, and the value of these areas for livestock. It can be difficult for natural resource management practitioners, who may not observe the landscape regularly, to evaluate land condition and prescribe appropriate land management strategies. It is argued that the participation of pastoralists in science and policy development is fundamental to achieving sustainable land management, providing opportunities for social learning within an adaptive management framework.
Response of grass species to different fire frequencies in semi-arid rangelands of central Argentina
Authors: Peláez Daniel V. , Andrioli Romina J. , Elia Omar R. , Bontti Eliana E. , Tomas María A. , Blazquez Francisco R.
Published: September 2013

The study was undertaken to quantify the effect of different controlled fire frequencies on foliar cover, density, individual basal area, and mortality of the most common perennial grass species in the semi-arid rangelands of the southern Caldenal in central Argentina over a 20-year period. Cover of bare soil was also assessed. The study comprised three fire treatments: (i) high fire frequency (controlled burns every 3–5 years; HFF); (ii) low fire frequency (controlled burns every 8 years; LFF); and (iii) unburned control (C). Fire treatments, regardless of frequency, induced an increase in foliar cover and density in desirable grasses, no changes in intermediate grasses, and a decrease in undesirable grasses. Individual basal area tended to be higher for desirable grasses and lower for intermediate and undesirable grasses when subject to fire. Most of the species under study exhibited higher mortality rates in the HFF treatment than in the LFF and C treatments. The results of the study suggest that recurrent controlled burns of moderate intensity may favour the herbage production of desirable perennial grasses. This, in turn, assuming appropriate grazing management, may have a beneficial impact on livestock production. Nevertheless, given the effects of fire on the cover of bare soil and mortality of grasses, further research is needed in order to determine the appropriate fire frequency in terms of rangeland sustainability.
Activity of striatal neurons reflects social action and own reward
Authors: Báez-Mendoza Raymundo , Harris Christopher J. , Schultz Wolfram
Published: September 2013

Significance

A basic requirement for engaging in beneficial social interactions is to recognize the actor whose movement results in reward. We studied the neuronal correlates of social action and reward in the monkey striatum. Behaviorally, the animals distinguished between their own and their conspecific's reward and knew which individual acted. In a subset of striatal neurons, neuronal activity occurred preferentially when either the own or the conspecific's action was followed by own reward. Some of the social action activity disappeared when the conspecific's role was simulated by a computer, confirming a social rather than observational relationship. These findings demonstrate a role of striatal neurons in identifying the social actor and own reward in a social setting.
Sleep spindles in midday naps enhance learning in preschool children
Authors: Kurdziel Laura , Duclos Kasey , Spencer Rebecca M. C.
Published: September 2013

Significance

Lacking scientific understanding of the function of naps in early childhood, policy makers may curtail preschool classroom nap opportunities due to increasing curriculum demands. Here we show evidence that classroom naps support learning in preschool children by enhancing memories acquired earlier in the day as compared with equivalent intervals spent awake.
Iceberg discharges of the last glacial period driven by oceanic circulation changes
Authors: Alvarez-Solas Jorge , Robinson Alexander , Montoya Marisa , Ritz Catherine
Published: September 2013

Significance

Periodic episodes of massive iceberg discharges from the large Northern Hemispheric ice sheets into the North Atlantic Ocean occurred throughout the last glacial cycle. It is still not clear whether they resulted from internal ice dynamics alone or were possibly externally driven. Results of our simulations of the Laurentide Ice Sheet forced by oceanic circulation changes support the hypothesis that these ice discharges were induced by the collapse of a buttressing ice shelf and the subsequent acceleration of inland ice streams. This provides a new basis for understanding the dynamics of the coupled cryosphere–climate system of glacial cycles. Additionally, it has strong implications for the stability of the marine parts of the Antarctic ice sheet given anthropogenic oceanic warming.
A transformation for the mechanical fingerprints of complex biomolecular interactions
Authors: Zhang Yaojun , Dudko Olga K.
Published: September 2013

Significance

A conversion between macromolecular shapes—a conformational change—is usually the mechanism that gives function to biological macromolecules. Single-molecule force spectroscopy probes conformational changes by applying force to individual macromolecules and recording their response, or “mechanical fingerprints”, in the form of force–extension curves. The mechanical fingerprints of proteins, nucleic acids, and their assemblies often feature elaborate signatures that reflect the complexity of the underlying biomolecular interactions. This study introduces a transformation that converts—in a model-free way—the mechanical fingerprints of a complex system into a map of force-dependent transition rates. Once transformed into a rate map, the mechanical fingerprints can be interpreted in terms of the activation barriers and the intrinsic timescales of a biological process.
Postsynaptic neural activity regulates neuronal addition in the adult avian song control system
Authors: Larson Tracy A. , Wang Tsu-Wei , Gale Samuel D. , Miller Kimberly E. , Thatra Nivretta M. , Caras Melissa L. , Perkel David J. , Brenowitz Eliot A.
Published: September 2013

Significance

Neural activity in the adult brain plays a key role in mediating experience-dependent neural plasticity. We show that inhibiting electrical activity in the song nucleus, robust nucleus of the arcopallium, in adult bird brain decreases the number of new projection neurons added to the afferent nucleus HVC. Our results are consistent with the general principle of activity-based target selection of newborn neurons during nervous system development and support the idea that developmental and adult plasticity exploit similar mechanisms. Understanding mechanisms influencing the incorporation of new neurons into established neural circuits in adult brains is critical for our basic understanding of neural plasticity and for exploiting the clinical potential of neuronal replacement to repair damage associated with injury and neurodegenerative diseases.
Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study
Authors: Carroll Judith E. , Gruenewald Tara L. , Taylor Shelley E. , Janicki-Deverts Denise , Matthews Karen A. , Seeman Teresa E.
Published: September 2013

Significance

Adverse social relations in early life are thought to negatively influence health throughout the lifespan. The present findings provide a biological link regarding why negative early life experiences affect health and further suggest that a loving parental figure may provide protection. It is well recognized that providing children in adverse circumstances with a nurturing relationship is beneficial for their overall wellbeing. Our findings suggest that a loving relationship may also prevent the rise in biomarkers indicative of disease risk across numerous physiological systems, impacting adverse health outcomes decades later. The results contribute in a meaningful way to several biological literatures and to the social sciences and, as such, will have a substantial impact.
Crystalline polymorphism induced by charge regulation in ionic membranes
Authors: Leung Cheuk-Yui , Palmer Liam C. , Kewalramani Sumit , Qiao Baofu , Stupp Samuel I. , Olvera de la Cruz Monica , Bedzyk Michael J.
Published: September 2013

Significance

The crystallization of molecules with polar and hydrophobic groups, such as ionic amphiphiles and proteins, is of paramount importance in biology and biotechnology. This combined X-ray scattering and theoretical study demonstrates how crystalline order within membranes formed by coassembled cationic and anionic amphiphiles can be controlled by varying pH and molecular tail length. Our work suggests design of bilayer membranes with specific crystalline arrangements at ambient temperature and physiologically relevant pH environments with suitable choice of headgroup and tail. Changes in crystallinity are likely to affect molecular diffusion rates across membranes and may enable control over the encapsulation and release of molecules within the membrane. Moreover, pH-induced crystalline transformations are likely used by organisms to control metabolic flow in harsh environments.
Structure and nucleic acid binding activity of the nucleoporin Nup157
Authors: Seo Hyuk-Soo , Blus Bartlomiej J. , Janković Nina Z. , Blobel Günter
Published: September 2013

Significance

The nuclear pore complex (NPC) is a multiprotein gating complex that allows for bidirectional transport across the nuclear membrane. A key feature of the NPC is a central transport channel that can undergo regulated diameter changes, thus enabling the trafficking of cargo of various sizes. Surrounding this channel is a group of proteins, named “adaptor” nucleoporins, which are envisioned to accommodate and orchestrate these structural changes. Here we show the crystal structure of a fragment of an adaptor nucleoporin, Nup157, which forms a compact C-shaped architecture. Notably, Nup157 contains a positively charged surface consistent with its nucleic acid binding capacity. Furthermore, the predicted hinge regions in Nup157 suggest its flexibility in agreement with the plastic nature of the NPC.
Designing Documents for Selective Reading
Authors: Farkas David K. , Raleigh Christopher
Published: September 2013

There are strong indications that many people increasingly resist reading medium-to-long documents. It is therefore important to contribute to the long-term viability of longer documents by providing better support for selective reading. Readers may be more willing to read longer documents knowing they have ample and near-seamless choices regarding which topics they can read and the level of detail at which they can read a particular topic. To design for selective reading requires an understanding of how readers deal with incomplete information and the concepts of prerequisite information and dependency relationships. Three broad approaches can be identified: building supported reading pathways, modularization, and summarization.
Tailoring fear appeals to lower-educated adolescents: The influence of modality and type of threat?
Authors: Burgers Christian , Veldhuis Jolanda
Published: September 2013

Research on smoking behavior suggests that less well-educated adolescents are most susceptible to taking up smoking. This paper reports on an experiment that investigates the effects of adapting fear appeals to this target group. Threats were manipulated in terms of content (long-term health versus short-term cosmetic effects) and form (image versus text). Results demonstrated that, for long-term health fear appeals, text was considered as easier, and was better understood and evaluated, than image. These results illustrate the advantage of using fear texts over fear images when targeting less well-educated adolescents and the importance of adapting anti-smoking advertisements to this group.
A Comparison of the Usability of Heuristic Evaluations for Online Help
Authors: Wallace Steve , Reid Adrian , Jin-Su Kang  , Clinciu Daniel
Published: September 2013

This study compares the usability of a general heuristic evaluation to that of a domain-specific heuristic evaluation focused on technical documentation. Eight technical writers used both heuristic evaluations to identify usability problems in an online help application. The validity of the usability problems they identified was ascertained by user testing. No significant difference was found in overall effectiveness or efficiency. However, writers indicated greater satisfaction with the general heuristic evaluation, while the domain-specific heuristic evaluation was more effective in some categories and showed greater inter-rater agreement. Results suggest that differences in effectiveness were related to the level of detail of the heuristics. This study therefore recommends the incorporation of more detailed heuristics into heuristic evaluations.
Bridging the Semantic Gap - An Approach based on Observations in Medical Research and Evidence-Based Clinical Practice
Authors: Sheydin André , Vella Gustav
Published: September 2013

Formal medical modeling is the basis for the systematic acquisition and analysis of medical data with the critical goals of reaching informed decisions in treatment and performing meaningful clinical research. While the semantic web provides a promising technology, the user experience of formal modeling remains largely unaddressed. Starting out from the view that evidence and knowledge presentation have a fundamental role in knowledge elicitation, an argument is made that working backwards from the goals which information systems strive to fulfill, the end user applications and the genuine context they provide, towards the underlying formalisms can lead to new and more accessible approaches in formal knowledge modeling.
A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton
Authors: Horn Henning F. , Kim Dae In , Wright Graham D. , Wong Esther Sook Miin , Stewart Colin L. , Burke Brian , Roux Kyle J.
Published: September 2013

Chromosome pairing is an essential meiotic event that ensures faithful haploidization and recombination of the genome. Pairing of homologous chromosomes is facilitated by telomere-led chromosome movements and formation of a meiotic bouquet, where telomeres cluster to one pole of the nucleus. In metazoans, telomere clustering is dynein and microtubule dependent and requires Sun1, an inner nuclear membrane protein. Here we provide a functional analysis of KASH5, a mammalian dynein-binding protein of the outer nuclear membrane that forms a meiotic complex with Sun1. This protein is related to zebrafish futile cycle (Fue), a nuclear envelope (NE) constituent required for pronuclear migration. Mice deficient in this Fue homologue are infertile. Males display meiotic arrest in which pairing of homologous chromosomes fails. These findings demonstrate that telomere attachment to the NE is insufficient to promote pairing and that telomere attachment sites must be coupled to cytoplasmic dynein and the microtubule system to ensure meiotic progression.
Independence of symmetry breaking on Bem1-mediated autocatalytic activation of Cdc42
Authors: Smith Sarah E. , Rubinstein Boris , Mendes Pinto Inês , Slaughter Brian D. , Unruh Jay R. , Li Rong
Published: September 2013

The ability to break symmetry and polarize through self-organization is a fundamental feature of cellular systems. A prevailing theory in yeast posits that symmetry breaking occurs via a positive feedback loop, wherein the adaptor protein Bem1 promotes local activation and accumulation of Cdc42 by directly tethering Cdc42GTP with its guanine nucleotide exchange factor (GEF) Cdc24. In this paper, we find that neither Bem1 nor the ability of Bem1 to bind Cdc42GTP is required for cell polarization. Instead, Bem1 functions primarily by boosting GEF activity, a role critical for polarization without actin filaments. In the absence of actin-based transport, polarization of Cdc42 is accomplished through Rdi1, the Cdc42 guanine nucleotide dissociation inhibitor. A mathematical model is constructed describing cell polarization as a product of distinct pathways controlling Cdc42 activation and protein localization. The model predicts a nonmonotonic dependence of cell polarization on the concentration of Rdi1 relative to that of Cdc42.
Notchless-dependent ribosome synthesis is required for the maintenance of adult hematopoietic stem cells
Authors: Le Bouteiller Marie , Souilhol Céline , Beck-Cormier Sarah , Stedman Aline , Burlen-Defranoux Odile , Vandormael-Pournin Sandrine , Bernex Florence , Cumano Ana , Cohen-Tannoudji Michel
Published: September 2013

Blood cell production relies on the coordinated activities of hematopoietic stem cells (HSCs) and multipotent and lineage-restricted progenitors. Here, we identify Notchless (Nle) as a critical factor for HSC maintenance under both homeostatic and cytopenic conditions. Nle deficiency leads to a rapid and drastic exhaustion of HSCs and immature progenitors and failure to maintain quiescence in HSCs. In contrast, Nle is dispensable for cycling-restricted progenitors and differentiated cells. In yeast, Nle/Rsa4 is essential for ribosome biogenesis, and we show that its role in pre-60S subunit maturation has been conserved in the mouse. Despite its implication in this basal cellular process, Nle deletion affects ribosome biogenesis only in HSCs and immature progenitors. Ribosome biogenesis defects are accompanied by p53 activation, which causes their rapid exhaustion. Collectively, our findings establish an essential role for Nle in HSC and immature progenitor functions and uncover previously unsuspected differences in ribosome biogenesis that distinguish stem cells from restricted progenitor populations.
Inappropriate Testing for Urinary Tract Infection in Hospitalized Patients: An Opportunity for Improvement
Authors: Hartley Sarah , Valley Staci , Kuhn Latoya , Washer Laraine L. , Gandhi Tejal , Meddings Jennifer , Chenoweth Carol , Malani Anurag N. , Saint Sanjay , Srinivasan Arjun , Flanders Scott A.
Published: September 2013

Urine cultures are frequently obtained for hospitalized patients. We reviewed documented indications for culture and compared these with professional society guidelines. Lack of documentation and important clinical scenarios (before orthopedic procedures and when the patient has altered mental status without a urinary catheter) are highlighted as areas of use outside of current guidelines.
Laboratory-Confirmed Influenza B Infection in Immunized Long-Term Care Facility Residents Receiving Oseltamivir Prophylaxis in Ontario
Authors: Winter Anne-Luise , Peci Adriana , Eshaghi AliReza , Baird Michelle , Memari Nader , Kristjanson Erik , Balogun Elizabeth , Higgins Rachel R. , Li Aimin , Farrell David J. , Gubbay Jonathan B.
Published: September 2013

We report on an influenza B outbreak in an Ontario long-term care facility in which 2 immunized residents receiving oseltamivir prophylaxis for at least 5 days developed laboratory-confirmed influenza B infection. All isolates were tested for the most common oseltamivir resistance, and none of them had resistance identified.
Outbreak of Joint Infections Associated with Magnetic Resonance Arthrograms Performed at an Outpatient Radiology Center
Authors: Kim Moon , Tyson Clara , Mascola Laurene
Published: September 2013

An outbreak of methicillin-susceptible Staphylococcus aureus joint infections occurred at an outpatient radiology center. We identified 7 case patients; all had undergone magnetic resonance arthrograms with intra-articular joint injections. The outbreak was likely due to unsafe injection practices in preparation of contrast solution for intra-articular injection.
Factors Associated with Hand Hygiene Compliance at a Tertiary Care Teaching Hospital
Authors: Kowitt Benjamin , Jefferson Julie , Mermel Leonard A.
Published: September 2013

Objective.

To identify factors associated with hand hygiene compliance during a multiyear period of intervention.

Design.

Observational study.

Setting.

A 719-bed tertiary care teaching hospital.

Participants.

Nursing, physician, technical, and support staff.

Methods.

Light-duty staff performed hand hygiene observations during the period July 2008-December 2012. Infection control implemented hospital-wide hand hygiene initiatives, including education modules; posters and table tents; feedback to units, medical directors and the executive board; and an increased number of automated alcohol hand hygiene product dispensers.

Results.

There were 161,526 unique observations; overall compliance was 83%. Significant differences in compliance were observed between physician staff (78%) and support staff (69%) compared with nursing staff (84%). Pediatric units (84%) and intensive care units (84%) had higher compliance than did medical (82%) and surgical units (81%). These findings persisted in the controlled multivariate model for noncompliance. Additional factors found to be significant in the model included greater compliance when healthcare workers were leaving patient rooms, when the patient was under contact precautions, and during the evening shift. The overall rate of compliance increased from 60% in the first year of observation to a peak of 96% in the fourth year, and it decreased to 89% in the final year, with significant improvements occurring in each of the 4 professional categories.

Conclusions.

A multipronged hand hygiene initiative is effective in increasing compliance rates among all categories of hospital workers. We identified a variety of factors associated with increased compliance. Additionally, we note the importance of continuous interventions in maintaining high compliance rates.
The rational cohomology of a 𝑝-local compact group
Authors: Broto C. , Levi R. , Oliver B.
Published: September 2013

For any prime

p
p

, the theory of

p
p

-local compact groups is modelled on the

p
p

-local homotopy theory of classifying spaces of compact Lie groups and

p
p

-compact groups and generalises the earlier concept of

p
p

-local finite groups. These objects have maximal tori and Weyl groups, although the Weyl groups need not be generated by pseudoreflections. In this paper, we study the rational

p
p

-adic cohomology of the classifying space of a

p
p

-local compact group and prove that just as for compact Lie groups, it is isomorphic to the ring of invariants of the Weyl group action on the cohomology of the classifying space of the maximal torus. This is applied to show that unstable Adams operations on

p
p

-local compact groups are determined in the appropriate sense by the map they induce on rational cohomology.
BOOK REVIEW
Authors: Klip IJsbrand T.
Published: September 2013

Heart Failure: A Practical Guide for Diagnosis and Management (Oxford American Cardiology Library) by Stuart Katz. Oxford University Press, UK, 2013. ISBN: 978‐0‐19‐991708‐2
Inexact trajectory planning and inverse problems in the Hamilton–Pontryagin framework
Authors: Burnett Christopher L. , Holm Darryl D. , Meier David M.
Published: September 2013

We study a trajectory-planning problem whose solution path evolves by means of a Lie group action and passes near a designated set of target positions at particular times. This is a higher-order variational problem in optimal control, motivated by potential applications in computational anatomy and quantum control. Reduction by symmetry in such problems naturally summons methods from Lie group theory and Riemannian geometry. A geometrically illuminating form of the Euler–Lagrange equations is obtained from a higher-order Hamilton–Pontryagin variational formulation. In this context, the previously known node equations are recovered with a new interpretation as Legendre–Ostrogradsky momenta possessing certain conservation properties. Three example applications are discussed as well as a numerical integration scheme that follows naturally from the Hamilton–Pontryagin principle and preserves the geometric properties of the continuous-time solution.
Symmetry breaking and polarity establishment during mouse oocyte maturation
Authors: Yi Kexi , Rubinstein Boris , Li Rong
Published: September 2013

Mammalian oocyte meiosis encompasses two rounds of asymmetric divisions to generate a totipotent haploid egg and, as by-products, two small polar bodies. Two intracellular events, asymmetric spindle positioning and cortical polarization, are critical to such asymmetric divisions. Actin but not microtubule cytoskeleton has been known to be directly involved in both events. Recent work has revealed a positive feedback loop between chromosome-mediated cortical activation and the Arp2/3-orchestrated cytoplasmic streaming that moves chromosomes. This feedback loop not only maintains meiotic II spindle position during metaphase II arrest, but also brings about symmetry breaking during meiosis I. Prior to an Arp2/3-dependent phase of fast movement, meiotic I spindle experiences a slow and non-directional first phase of migration driven by a pushing force from Fmn2-mediated actin polymerization. In addition to illustrating these molecular mechanisms, mathematical simulations are presented to elucidate mechanical properties of actin-dependent force generation in this system.
Actin polymerization or myosin contraction: two ways to build up cortical tension for symmetry breaking
Authors: Carvalho Kevin , Lemière Joël , Faqir Fahima , Manzi John , Blanchoin Laurent , Plastino Julie , Betz Timo , Sykes Cécile
Published: September 2013

Cells use complex biochemical pathways to drive shape changes for polarization and movement. One of these pathways is the self-assembly of actin filaments and myosin motors that together produce the forces and tensions that drive cell shape changes. Whereas the role of actin and myosin motors in cell polarization is clear, the exact mechanism of how the cortex, a thin shell of actin that is underneath the plasma membrane, can drive cell shape changes is still an open question. Here, we address this issue using biomimetic systems: the actin cortex is reconstituted on liposome membranes, in an ‘outside geometry’. The actin shell is either grown from an activator of actin polymerization immobilized at the membrane by a biotin–streptavidin link, or built by simple adsorption of biotinylated actin filaments to the membrane, in the presence or absence of myosin motors. We show that tension in the actin network can be induced either by active actin polymerization on the membrane via the Arp2/3 complex or by myosin II filament pulling activity. Symmetry breaking and spontaneous polarization occur above a critical tension that opens up a crack in the actin shell. We show that this critical tension is reached by growing branched networks, nucleated by the Arp2/3 complex, in a concentration window of capping protein that limits actin filament growth and by a sufficient number of motors that pull on actin filaments. Our study provides the groundwork to understanding the physical mechanisms at work during polarization prior to cell shape modifications.
Actin dynamics rapidly reset chemoattractant receptor sensitivity following adaptation in neutrophils
Authors: Dandekar Sheel N. , Park Jason S. , Peng Grace E. , Onuffer James J. , Lim Wendell A. , Weiner Orion D.
Published: September 2013

Neutrophils are cells of the innate immune system that hunt and kill pathogens using directed migration. This process, known as chemotaxis, requires the regulation of actin polymerization downstream of chemoattractant receptors. Reciprocal interactions between actin and intracellular signals are thought to underlie many of the sophisticated signal processing capabilities of the chemotactic cascade including adaptation, amplification and long-range inhibition. However, with existing tools, it has been difficult to discern actin's role in these processes. Most studies investigating the role of the actin cytoskeleton have primarily relied on actin-depolymerizing agents, which not only block new actin polymerization but also destroy the existing cytoskeleton. We recently developed a combination of pharmacological inhibitors that stabilizes the existing actin cytoskeleton by inhibiting actin polymerization, depolymerization and myosin-based rearrangements; we refer to these processes collectively as actin dynamics. Here, we investigated how actin dynamics influence multiple signalling responses (PI3K lipid products, calcium and Pak phosphorylation) following acute agonist addition or during desensitization. We find that stabilized actin polymer extends the period of receptor desensitization following agonist binding and that actin dynamics rapidly reset receptors from this desensitized state. Spatial differences in actin dynamics may underlie front/back differences in agonist sensitivity in neutrophils.
Roles of Rho GTPases in leucocyte and leukaemia cell transendothelial migration
Authors: Infante Elvira , Ridley Anne J.
Published: September 2013

Leucocytes migrate into and out of blood vessels at multiple points during their development and maturation, and during immune surveillance. In response to tissue damage and infection, they are rapidly recruited through the endothelium lining blood vessels into the tissues. Leukaemia cells also move in and out of the bloodstream during leukaemia progression. Rho GTPases are intracellular signalling proteins that regulate cytoskeletal dynamics and are key coordinators of cell migration. Here, we describe how different members of the Rho GTPase family act in leucocytes and leukaemia cells to regulate steps of transendothelial migration. We discuss how inhibitors of Rho signalling could be used to reduce leucocyte or leukaemia cell entry into tissues.
p120catenin alteration in cancer and its role in tumour invasion
Authors: Peglion Florent , Etienne-Manneville Sandrine
Published: September 2013

Since its discovery in 1989 as a substrate of the Src oncogene, p120catenin has been revealed as an important player in cancer initiation and tumour dissemination. p120catenin regulates a wide range of cellular processes such as cell–cell adhesion, cell polarity and cell proliferation and plays a pivotal role in morphogenesis, inflammation and innate immunity. The pleiotropic effects of p120catenin rely on its interactions with numerous partners such as classical cadherins at the plasma membrane, Rho-GTPases and microtubules in the cytosol and transcriptional modulators in the nucleus. Alterations of p120catenin in cancer not only concern its expression level but also its intracellular localization and can lead to both pro-invasive and anti-invasive effects. This review focuses on the p120catenin-mediated pathways involved in cell migration and invasion and discusses the potential consequences of major cancer-related p120catenin alterations with respect to tumour spread.
Functional genomics in the study of yeast cell polarity: moving in the right direction
Authors: Styles Erin , Youn Ji-Young , Mattiazzi Usaj Mojca , Andrews Brenda
Published: September 2013

The budding yeastSaccharomyces cerevisiaehas been used extensively for the study of cell polarity, owing to both its experimental tractability and the high conservation of cell polarity and other basic biological processes among eukaryotes. The budding yeast has also served as a pioneer model organism for virtually all genome-scale approaches, including functional genomics, which aims to define gene function and biological pathways systematically through the analysis of high-throughput experimental data. Here, we outline the contributions of functional genomics and high-throughput methodologies to the study of cell polarity in the budding yeast. We integrate data from published genetic screens that use a variety of functional genomics approaches to query different aspects of polarity. Our integrated dataset is enriched for polarity processes, as well as some processes that are not intrinsically linked to cell polarity, and may provide new areas for future study.
Epithelial polarity and spindle orientation: intersecting pathways
Authors: Bergstralh Dan T. , Haack Timm , St Johnston Daniel
Published: September 2013

During asymmetric stem cell divisions, the mitotic spindle must be correctly oriented and positioned with respect to the axis of cell polarity to ensure that cell fate determinants are appropriately segregated into only one daughter cell. By contrast, epithelial cells divide symmetrically and orient their mitotic spindles perpendicular to the main apical–basal polarity axis, so that both daughter cells remain within the epithelium. Work in the past 20 years has defined a core ternary complex consisting of Pins, Mud and Gαi that participates in spindle orientation in both asymmetric and symmetric divisions. As additional factors that interact with this complex continue to be identified, a theme has emerged: there is substantial overlap between the mechanisms that orient the spindle and those that establish and maintain apical–basal polarity in epithelial cells. In this review, we examine several factors implicated in both processes, namely Canoe, Bazooka, aPKC and Discs large, and consider the implications of this work on how the spindle is oriented during epithelial cell divisions.
Kolente virus, a rhabdovirus species isolated from ticks and bats in the Republic of Guinea
Authors: Ghedin Elodie , Rogers Matthew B. , Widen Steven G. , Guzman Hilda , Travassos da Rosa Amelia P. A. , Wood Thomas G. , Fitch Adam , Popov Vsevolod , Holmes Edward C. , Walker Peter J. , Vasilakis Nikos , Tesh Robert B.
Published: September 2013

Kolente virus (KOLEV) is a rhabdovirus originally isolated from ticks and a bat in Guinea, West Africa, in 1985. Although tests at the time of isolation suggested that KOLEV is a novel rhabdovirus, it has remained largely uncharacterized. We assembled the complete genome sequence of the prototype strain DakAr K7292, which was found to encode the five canonical rhabdovirus structural proteins (N, P, M, G and L) with alternative ORFs (>180 nt) in the P and L genes. Serologically, KOLEV exhibited a weak antigenic relationship with Barur and Fukuoka viruses in the Kern Canyon group. Phylogenetic analysis revealed that KOLEV represents a distinct and divergent lineage that shows no clear relationship to any rhabdovirus except Oita virus, although with limited phylogenetic resolution. In summary, KOLEV represents a novel species in the family Rhabdoviridae.
An insulin-like growth factor homologue of Singapore grouper iridovirus modulates cell proliferation, apoptosis and enhances viral replication
Authors: Yan Yang , Cui Huachun , Guo Chuanyu , Li Jun , Huang Xiaohong , Wei Jingguang , Qin Qiwei
Published: September 2013

Insulin-like growth factors (IGFs) play crucial roles in regulating cell differentiation, proliferation and apoptosis. In this study, a novel IGF homologue gene (IGF-like) encoded by Singapore grouper iridovirus (SGIV) ORF062R (termedSGIV–IGF), was cloned and characterized. The coding region ofSGIV–IGFis 771 bp in length, with a variable number of tandem repeats (VNTR) locus at the 3′-end. We cloned one isoform of this novel gene, 582 bp in length, containing the predicted IGF domain and 3.6 copy numbers of the 27 bp repeat unit.SGIV–IGFwas an early transcribed gene during viral infection, and SGIV–IGF was distributed predominantly in the cytoplasm with a diffused granular appearance. Intriguingly, overexpression of SGIV–IGF was able to promote the growth of grouper embryonic cells (GP cells) by promoting G1/S phase transition, which was at least partially dependent on its 3′-end VNTR locus. Furthermore, viral titre assay and real-time quantitative PCR (RT-qPCR) analysis proved that SGIV–IGF could promote SGIV replication in grouper cells. In addition, overexpression of SGIV–IGF mildly facilitated apoptosis in SGIV-infected non-host fathead minnow (FHM) cells. Together, our study demonstrated a novel functional gene of SGIV which may regulate viral replication and cellular processes through multiple mechanisms that appear to be cell type-dependent.
Microtubule depolymerization activates the Epstein–Barr virus lytic cycle through protein kinase C pathways in nasopharyngeal carcinoma cells
Authors: Liu Yi-Ru , Huang Sheng-Yen , Chen Jen-Yang , Wang Lily Hui-Ching
Published: September 2013

Elevated levels of antibodies against Epstein–Barr virus (EBV) and the presence of viral DNA in plasma are reliable biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC) in high-prevalence areas, such as South-East Asia. The presence of these viral markers in the circulation suggests that a minimal level of virus reactivation may have occurred in an infected individual, although the underlying mechanism of reactivation remains to be elucidated. Here, we showed that treatment with nocodazole, which provokes the depolymerization of microtubules, induces the expression of two EBV lytic cycle proteins, Zta and EA-D, in EBV-positive NPC cells. This effect was independent of mitotic arrest, as viral reactivation was not abolished in cells synchronized at interphase. Notably, the induction of Zta by nocodazole was mediated by transcriptional upregulation via protein kinase C (PKC). Pre-treatment with inhibitors for PKC or its downstream signalling partners p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) abolished the nocodazole-mediated induction of Zta and EA-D. Interestingly, the effect of nocodazole, as well as colchicine and vinblastine, on lytic gene expression occurred only in NPC epithelial cells but not in cells derived from lymphocytes. These results establish a novel role of microtubule integrity in controlling the EBV life cycle through PKC and its downstream pathways, which represents a tissue-specific mechanism for controlling the life-cycle switch of EBV.
De- and repolarization mechanism of flagellar morphogenesis during a bacterial cell cycle
Authors: Davis Nicole J. , Cohen Yaniv , Sanselicio Stefano , Fumeaux Coralie , Ozaki Shogo , Luciano Jennifer , Guerrero-Ferreira Ricardo C. , Wright Elizabeth R. , Jenal Urs , Viollier Patrick. H.
Published: September 2013

Eukaryotic morphogenesis is seeded with the establishment and subsequent amplification of polarity cues at key times during the cell cycle, often using (cyclic) nucleotide signals. We discovered that flagellum de- and repolarization in the model prokaryote Caulobacter crescentus is precisely orchestrated through at least three spatiotemporal mechanisms integrated at TipF. We show that TipF is a cell cycle-regulated receptor for the second messenger—bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)—that perceives and transduces this signal through the degenerate c-di-GMP phosphodiesterase (EAL) domain to nucleate polar flagellum biogenesis. Once c-di-GMP levels rise at the G1 → S transition, TipF is activated, stabilized, and polarized, enabling the recruitment of downstream effectors, including flagellar switch proteins and the PflI positioning factor, at a preselected pole harboring the TipN landmark. These c-di-GMP-dependent events are coordinated with the onset of tipF transcription in early S phase and together enable the correct establishment and robust amplification of TipF-dependent polarization early in the cell cycle. Importantly, these mechanisms also govern the timely removal of TipF at cell division coincident with the drop in c-di-GMP levels, thereby resetting the flagellar polarization state in the next cell cycle after a preprogrammed period during which motility must be suspended.
Induction of sarcomas by mutant IDH2
Authors: Lu Chao , Venneti Sriram , Akalin Altuna , Fang Fang , Ward Patrick S. , DeMatteo Raymond G. , Intlekofer Andrew M. , Chen Chong , Ye Jiangbin , Hameed Meera , Nafa Khedoudja , Agaram Narasimhan P. , Cross Justin R. , Khanin Raya , Mason Christopher E. , Healey John H. , Lowe Scott W. , Schwartz Gary K. , Melnick Ari , Thompson Craig B.
Published: September 2013

More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions. Regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification. In murine 10T1/2 mesenchymal progenitor cells, expression of mutant IDH2 led to DNA hypermethylation and an impairment in differentiation that could be reversed by treatment with DNA-hypomethylating agents. Introduction of mutant IDH2 also induced loss of contact inhibition and generated undifferentiated sarcomas in vivo. The oncogenic potential of mutant IDH2 correlated with the ability to produce 2-hydroxyglutarate. Together, these data demonstrate that neomorphic IDH2 mutations can be oncogenic in mesenchymal cells.
Small RNA profiling of Xenopus embryos reveals novel miRNAs and a new class of small RNAs derived from intronic transposable elements
Authors: Harding Joanne L. , Horswell Stuart , Heliot Claire , Armisen Javier , Zimmerman Lyle B. , Luscombe Nicholas M. , Miska Eric A. , Hill Caroline S.
Published: September 2013

Small RNA control of gene expression is critical for developmental processes in vertebrate embryos. To determine the dynamics of small RNA expression and to uncover novel small RNAs in the early vertebrate embryo, we performed high-throughput sequencing of all small RNAs in Xenopus tropicalis embryos at three developmental time points and in dissected halves of gastrula embryos. This analysis allowed us to identify novel microRNAs and we show that microRNA expression is highly dynamic and spatially localized in early embryos. In addition, we have developed a microRNA prediction pipeline and demonstrate that it has the power to predict new miRNAs that are experimentally detectable in frogs, mice, and humans. By combining the small RNA sequencing with mRNA profiling at the different developmental stages, we identify a new class of small noncoding RNAs that we name siteRNAs, which align in clusters to introns of protein-coding genes. We show that siteRNAs are derived from remnants of transposable elements present in the introns. We find that genes containing clusters of siteRNAs are transcriptionally repressed as compared with all genes. Furthermore, we show that this is true for individual genes containing siteRNA clusters, and that these genes are enriched in specific repressive histone modifications. Our data thus suggest a new mechanism of siteRNA-mediated gene silencing in vertebrates, and provide an example of how mobile elements can affect gene regulation.