bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pacific‐Atlantic seesaw and the Bering Strait
Authors: Hu Aixue , Meehl Gerald A. , Han Weiqing , Abe‐Ouchi Ayako , Morrill Carrie , Okazaki Yusuke , Chikamoto Megume O.
Published: January 2012

Paleo proxy data and previous modeling studies both indicate that the massive discharge of icebergs into the North Atlantic may have led to a (nearly) collapsed Atlantic meridional overturning circulation (AMOC), resulting in a seesaw‐like climate change between the North Pacific and North Atlantic, with a warming in the former and a cooling in the latter. Here by using a fully coupled climate model, we show that this Pacific‐Atlantic seesaw associated with changes of the AMOC can only occur when the Bering Strait is closed. As this strait is closed, the oceanic communication between the North Pacific and Atlantic is cut off. When AMOC collapses, the North Atlantic becomes cooler, but the North Pacific becomes warmer due to the buildup of the Pacific meridional overturning circulation which transports more warm and salty subtropical water into the North Pacific, leading to seesaw‐like climate changes in the two ocean basins.
Rapid acceleration of radiation belt energetic electrons by Z‐mode waves
Authors: Xiao Fuliang , Zhang Sai , Su Zhenpeng , He Zhaoguo , Tang Lijun
Published: January 2012

We present the first simulation of the effect of Z‐mode waves on the outer radiation belt electron dynamics. We calculate bounce‐averaged diffusion rates in pitch angle and momentum and then use them as inputs to solve a 2‐D momentum‐pitch angle diffusion equation. Numerical results show that the phase space density (PSD) of 1 MeV electrons can enhance substantially and very rapidly (e.g., 30 minutes). In particular, the momentum diffusion rate exceeds the pitch angle and cross diffusion rates at 0.5 MeV and above, a behavior completely different from that for EMIC and chorus waves. Consequently, momentum (instead of pitch angle or cross) diffusion plays a dominant role in the dynamic evolution of energetic electrons. Moreover, the PSD evolution is found to be very dependent upon the assumed initial particle distributions. These results provide further insights on the interplay between acceleration mechanisms of outer radiation belt electrons.
Spectral induced polarization of shaly sands: Influence of the electrical double layer
Authors: Revil A.
Published: January 2012

I developed a new model named POLARIS describing the complex conductivity of (pyrite‐free) shaly poorly sorted sands. This model is based on the solution given by the effective medium theory for grains coated by an electrical double layer and immersed in a background electrolyte. The electrical double layer comprises the Stern layer and the diffuse layer. Both layers play very distinct roles in the in‐phase and quadrature conductivities. The polarization of the shaly sands is mainly controlled by the polarization of the Stern layer (except at very high salinities) with a very small mobility of the counterions contained in this layer. The in‐phase component of the conductivity is controlled by the conductivity of the pore water with a contribution associated with the diffuse layer (the contribution of the Stern layer seems negligible). The fraction of counterions in the Stern layer is computed from a simple sorption isotherm and is used to infer the quadrature conductivity. The quadrature conductivity is assumed to be frequency independent, which is a reasonable approximation in clayey sands and sandstones, in agreement with observations. The polarization model is also based on the assumption that the Stern layer is discontinuous between grains, an assumption that is consistent with recent models of ionic transport in clayey sands. POLARIS explains the dependence of the quadrature conductivity on the salinity, cation exchange capacity, specific surface area (or specific surface per unit pore volume), and temperature. It can be used to predict the saturation and the permeability (inside 1 order of magnitude).
A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3)
Authors: Fuller Stephen J. , McGuffin Liam J. , Marshall Andrew K. , Giraldo Alejandro , Pikkarainen Sampsa , Clerk Angela , Sugden Peter H.
Published: January 2012

The canonical pathway of regulation of the GCK (germinal centre kinase) III subgroup member, MST3 (mammalian Sterile20-related kinase 3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr178), induction of serine/threonine protein kinase activity and nuclear localization. We identified an alternative ‘non-canonical’ pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein GOLGA2/gm130 (golgin A2/Golgi matrix protein 130). Activation of MST3 by calyculin A (a protein serine/threonine phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr178) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr328) in the regulatory domain, an event also requiring the MST3(341–376) sequence which acts as a putative docking domain. MST3(Thr178) phosphorylation increased MST3 kinase activity, but this activity was independent of MST3(Thr328) phosphorylation. Interestingly, MST3(Thr328) lies immediately C-terminal to a STRAD (Sterile20-related adaptor) pseudokinase-like site identified recently as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr178/Thr328) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr328) phosphorylation was necessary for formation of the activated MST3–MO25 holocomplex.
Intensive Voice Treatment (LSVT LOUD) for Children With Spastic Cerebral Palsy and Dysarthria
Authors: Fox Cynthia Marie , Boliek Carol Ann
Published: January 2012

Purpose

The purpose of this study was to examine the effects of an intensive voice treatment (Lee Silverman Voice Treatment, commonly known as LSVT LOUD) for children with spastic cerebral palsy (CP) and dysarthria.

Method

A nonconcurrent multiple baseline single-subject design with replication across 5 children with spastic CP was used. Auditory–perceptual analysis of speech, acoustic measures of vocal functioning, and perceptual ratings by parents of participants were obtained at baseline, posttreatment, and 6-week follow-up recording sessions.

Results

Listeners consistently preferred the speech samples taken immediately posttreatment over those taken during the baseline phase for most perceptual characteristics rated in this study. Changes in acoustic measures of vocal functioning were not consistent across participants and occurred more frequently for maximum performance tasks as opposed to speech. Although parents of the treated participants reported an improved perception of vocal loudness immediately following treatment, maintenance of changes at 6-week follow-up varied across the participants. No changes were observed in the 5th participant, who did not receive treatment.

Conclusions

These findings provide some preliminary observations that the children with spastic CP in this study not only tolerated intensive voice treatment but also showed improvement on select aspects of vocal functioning. These outcomes warrant further research through Phase 2 treatment studies.
Sequence and System in the Acquisition of Tense and Agreement
Authors: Rispoli Matthew , Hadley Pamela A. , Holt Janet K.
Published: January 2012

Purpose

The relatedness of tense morphemes in the language of children younger than 3 years of age is a matter of controversy. Generativist accounts predict that the morphemes will be related, whereas usage-based accounts predict the absence of relationships. This study focused on the increasing productivity of the 5 morphemes in the tense productivity score (copula BE, third-person singular present –
3s,
past –
ed,
auxiliary DO, auxiliary BE; Hadley & Short, 2005) and their relationship to one another.

Method

Twenty typically developing children were observed longitudinally from 21 to 33 months of age. One hour of naturalistic caregiver–child interaction sampled every 3 months was analyzed.

Results

Copula BE was more productive than all other morphemes from age 27 months onward. Auxiliary BE was significantly less productive than –
3s,
–
ed,
and DO from age 27 months onward. Evaluation of third-person singular tense morphemes at age 33 months revealed that the productivity scores of copula
is,
–
3s,
and
does
were all correlated.

Conclusions

There is sequence and simultaneity in development that no prior framework has fully explained, as well as evidence of cross-morpheme relationships. In this article, the authors interpret these findings as support for the gradual morphosyntactic learning hypothesis (Rispoli & Hadley, 2011; Rispoli, Hadley, & Holt, 2009).
Development of Phonological Processing Skills in Children With Specific Language Impairment With and Without Literacy Delay: A 3-Year Longitudinal Study
Authors: Vandewalle Ellen , Boets Bart , Ghesquière Pol , Zink Inge
Published: January 2012

Purpose

To compare the development of phonological skills in children with specific language impairment (SLI) with and without literacy delay and to examine whether kindergarten phonological skills could discriminate these 2 groups.

Method

In a longitudinal study, 8 children with SLI and literacy delay, 10 children with SLI and normal literacy, and 14 typically developing children were studied from the last year of kindergarten to the start of Grade 3. A wide range of phonological tasks (phonological awareness [PA], verbal short-term memory [vSTM], and rapid automatized naming [RAN]) were administered yearly.

Results

The SLI group with literacy delay scored significantly lower than the typically developing children on almost all phonological tasks in all grades, whereas the SLI group with normal literacy scored significantly lower only on demanding PA and vSTM tasks. A combination of kindergarten PA and RAN skills could correctly classify 75% of the children with SLI. By including vSTM, the discriminatory value did not increase.

Conclusions

Children with SLI and normal literacy at age 8;1 [years;months] continued to have difficulties with demanding PA and vSTM tasks. Children with SLI and poor PA and RAN in kindergarten were at high risk of developing literacy problems in a transparent orthography.
Contribution of Family Environment to Pediatric Cochlear Implant Users' Speech and Language Outcomes: Some Preliminary Findings
Authors: Holt Rachael Frush , Beer Jessica , Kronenberger William G. , Pisoni David B. , Lalonde Kaylah
Published: January 2012

Purpose

To evaluate the family environments of children with cochlear implants and to examine relationships between family environment and postimplant language development and executive function.

Method

Forty-five families of children with cochlear implants completed a self-report family environment questionnaire (Family Environment Scale—Fourth Edition; Moos & Moos, 2009) and an inventory of executive function (Behavior Rating Inventory of Executive Function [Gioia, Isquith, Guy, & Kenworthy, 2000] or Behavior Rating Inventory of Executive Function—Preschool Version [Gioia, Espy, & Isquith, 2003]). The authors also evaluated children's receptive vocabulary (Peabody Picture Vocabulary Test—Fourth Edition; Dunn & Dunn, 2007) and global language skills (Preschool Language Scale—Fourth Edition [Zimmerman, Steiner, & Pond, 2002] and Clinical Evaluation of Language Fundamentals—Fourth Edition [Semel, Wiig, & Secord, 2003]).

Results

The family environments of children with cochlear implants differed from those of normal-hearing children but not in clinically significant ways. Language development and executive function were found to be atypical but not uncharacteristic of this clinical population. Families with higher levels of self-reported control had children with smaller vocabularies. Families reporting a higher emphasis on achievement had children with fewer executive function and working memory problems. Finally, families reporting a higher emphasis on organization had children with fewer problems related to inhibition.

Conclusion

Some of the variability in cochlear implantation outcomes that have protracted periods of development is related to family environment. Because family environment can be modified and enhanced by therapy or education, these preliminary findings hold promise for future work in helping families to create robust language-learning environments that can maximize their child's potential with a cochlear implant.
Indoor noise measurements evaluations for HVAC-Unit using
inter-laboratory comparisons
Authors: Seddeq H. S. , Medhat A. Fahim A.A.
Published: January 2012

The international standard, ISO/IEC 17025 was developed to determine technical competence
and to evaluate laboratories throughout the world. Accreditation bodies playing a vital
role are increasingly using proficiency testing methodology as a tool to ensure the
credibility of their accreditation programs. The successful completion of a well-designed
proficiency test can validate the measurement method and uncertainty budgets of a testing
laboratory. Additionally, proficiency tests can provide a good indication about the
quality of the test results. An important part of inter-laboratory comparisons and
proficiency testing is the determination of the associated error analyses which are
focused on uncertainty values. This paper presents the implementation of proficiency tests
using inter-laboratory methodology among five different acoustic laboratories. These tests
were carried out on 5.27 KWCooling standard unitary air conditioner, A/C, such
as through-wall or split room standard A/C units, for the assessment of Housing &
Building National Centre acoustic laboratory. Analyses of results show a good agreement
for En-Value among the selected laboratories
when compared with the lowest uncertainty as stated by proficiency tests standards.
Less Advanced Stages of Colon Cancer in Patients with Type 2 Diabetes Mellitus: an Unexpected Finding?
Authors: Nagel J. , Bücker S. , Wood M. , Stark R. , Göke B. , Parhofer K. , Allgayer H.
Published: January 2012

Epidemiological studies have found an increased risk for colon cancer and faster disease progression in patients with type 2 diabetes mellitus (T2DM). We aimed to determine whether patients with T2DM are diagnosed with more advanced stages of colorectal cancer, i. e., metastasized disease (UICC III and IV), at the time of diagnosis, since such a finding may have an impact on future guidelines for patients with T2DM.

A cross-sectional analysis of colorectal cancer patients was performed. Stages at diagnosis in patients with (18.0%) or without (82%) T2DM were compared using logistic regression analysis to correct for confounders.

Patients with T2DM were older, more obese, and more often male (each p<0.05). Unexpectedly, patients with T2DM had a lower risk for metastasized disease at diagnosis (p=0.023). Correction for age, gender, BMI, smoking and aspirin intake in a multiple logistic regression analysis did not change the result (OR=0.57, p=0.037). When looking at individual cancer stages rather than collapsed categories, there was a trend for less advanced stages in patients with T2DM (p=0.093). Excluding stage I because of potential screening bias due to the introduction of (insurance-covered) colonoscopy screening improved model fit, and confirmed less advanced cancer stages (p=0.0246).

Possibly because of earlier detection, patients with T2DM may be at lower risk for advanced stages of colon cancer at diagnosis. Further studies are warranted to confirm our results and to investigate the impact of closer medical surveillance in patients with type 2 diabetes mellitus.
The Dynamics of Client-Consultant Relationships: Exploring the Interplay of Power and Knowledge
Authors: Pozzebon Marlei , Pinsonneault Alain
Published: January 2012

In this paper, we investigate the dynamics of client-consultant relationships and analyze how power and knowledge are shared and negotiated between consultants and clients during the implementation of configurable technologies. Empirical evidence is provided by three case studies representing three classic types of client-consultant relationships. We draw on two complementary perspectives: possession view (i.e., power and knowledge are based on resources that can be owned or controlled by individuals) and practice view (i.e., power and knowledge are relational in nature and exercised in action). The paper develops a framework that shows that power and knowledge are closely intertwined and that the possession and practice views are complementary in understanding configurable technology projects. The paper also demonstrates the importance of the initial set-up of the project and how knowing/powering mechanisms can reinforce or change implementation trajectories, which, in turn, can affect project results.
Active control of the resistive wall mode with power saturation
Authors: Li Li , Liu Yue , Liu Yueqiang
Published: January 2012

An analytic model of non-linear feedback stabilization of the resistive wall mode is presented. The non-linearity comes from either the current or the voltage saturation of the control coil power supply. For the so-called flux-to-current control, the current saturation of active coils always results in the loss of control. On the contrary, the flux-to-voltage control scheme tolerates certain degree of the voltage saturation. The minimal voltage limit is calculated, below which the control will be lost.
Double-functionalized nanopore-embedded gold electrodes for rapid DNA sequencing
Authors: Pathak Biswarup , Löfås Henrik , Prasongkit Jariyanee , Grigoriev Anton , Ahuja Rajeev , Scheicher Ralph H.
Published: January 2012

We have studied the effect of double-functionalization on gold electrodes for improving nanopore-based DNA sequencing. The functionalizing molecular probes are, respectively, capable of temporarily forming hydrogen bonds with both the nucleobase part and the phosphate group of the target DNA, thus potentially minimizing the structural fluctuations of a single-stranded DNA molecule passing between the gold electrodes. The results of our first-principles study indicate that the proposed setup yields current signals that differ by at least 1 order of magnitude for the four different nucleic acid bases, thus offering the possibility to electrically distinguish them.
Spectroscopic study of white organic light-emitting devices with various thicknesses of emissive layer
Authors: Young Kim Woo , Kim You-Hyun , Jhun Chul-Gyu , Wood R. , Mascher P. , Moon C.-B.
Published: January 2012

White light-emitting devices based on a donor-acceptor structure were fabricated in order to investigate the dependence of the optical properties of white light emission on the thickness variance (15, 20, 25, and 30 nm) of the emissive layer. The emissive layer has a donor-acceptor system with the host 4,4′,4′′-tris(carbasol-l-nyl)triphenylamine molecule doped with 4,4′-bis(9-ethyl-3-carbazovinylene)-1,1′-biphenyl (BCzVBi) and 5,6,11,12-tetraphenylnaphtacene (Rubrene) molecules for blue and yellowish-green light activators, respectively. The characteristics of current density were analyzed by using a power function of applied field, J=σlEl+1 and the characteristic exponential function, J=J0(e(V-Vd)/V0-1). Through spectroscopic analysis, we obtained three physical quantities governing the device performance: 1) an effective conductivity, 2) a threshold potential, and 3) a characteristic potential barrier, which are associated with the trap-charge limited concentration in the bulk layer, the energy gap of the organic materials, and the barrier energy at the contact of electrodes, respectively. The electroluminescent spectra were studied quantitatively using a multi-peak fit with a Gaussian distribution for each electromagnetic transition. By this approach, we deduced the energy levels of the BCzVBi and Rubrene molecules that give leading information on the light emission mechanism and the energy transfer in the host-dopant system.
Electron detrapping in thin hafnium silicate and nitrided hafnium silicate gate dielectric stacks
Authors: Huang Heng-Sheng , Samanta Piyas , Tzeng Tsung-Jian , Chen Shuang-Yuan , Liu Chuan-Hsi
Published: January 2012

The kinetics of zero-field and field-induced detrapping of electrons trapped in HfSixOy and HfSiON after positive bias stress on n+-polycrystalline silicon (polySi) gate of n-type metal-oxide-semiconductor (nMOS) capacitors are experimentally investigated. The self detrapping follows a simple logarithmic relation with time while field-induced detrapping upon reversing the stress voltage obeys a simple first-order exponential decay suggesting mono energetic shallow traps associated with tunnel emission of trapped electrons. Finally, our investigation raises questions about the validity of the widely used distributed capture cross section model of electron traps to explain the threshold voltage instability in MOS devices with hafnium silicate gate stacks.
The roles of ruthenium nanoparticles decorated on thin multi-walled carbon nanotubes in the enhancement of field emission properties
Authors: Youb Lee Seung , Jeon Cheolho , Kim Yooseok , Chel Choi Won , Ihm Kyuwook , Kang Tai-Hee , Kim Young-Hwan , Keun Kim Chun , Park Chong-Yun
Published: January 2012

The roles of metal nanoparticles (NPs) decorated on carbon nanotubes (CNTs) in the enhancement of field emission properties were investigated by measuring the work functions (WF), densities of state (DOS), turn-on fields, current densities, and sizes of NPs. RuO2 was deposited on CNTs and reduced to Ru by annealing at elevated temperatures. The WF decreased during reduction, and integrated DOS increased after the formation of Ru NPs. Consequently, the turn-on field showed strong correlation with the WF, and the shape of the Ru NPs had a more significant impact on current density than the WF and DOS.
Monolayer graphene growth on Ni(111) by low temperature chemical vapor deposition
Authors: Addou Rafik , Dahal Arjun , Sutter Peter , Batzill Matthias
Published: January 2012

In contrast to the commonly employed high temperature chemical vapor deposition growth that leads to multilayer graphene formation by carbon segregation from the bulk, we demonstrate that below 600 °C graphene can be grown in a self-limiting monolayer growth process. Optimum growth is achieved at ∼550 °C. Above this temperature, carbon diffusion into the bulk is limiting the surface growth rate, while at temperatures below ∼500 °C a competing surface carbide phase impedes graphene formation.
Tuning of magnetization relaxation in ferromagnetic thin films through seed layers
Authors: Lu Lei , Young Jared , Wu Mingzhong , Mathieu Christoph , Hadley Matthew , Krivosik Pavol , Mo Nan
Published: January 2012

Tuning of the magnetization relaxation in Fe65Co35 thin films via seed layers was demonstrated. Through the use of different types of seed layers, one can tune substantially both the magnitude and frequency dependence of the relaxation rate η of the film. This tuning relies on the change of the film grain properties with the seed layer and the correlation between grain properties and two-magnon scattering processes. In spite of a significant change of η with the seed layer, the film static magnetic properties remain relatively constant.
Ferroelectric phase transition in strained multiferroic (Bi0.9La0.1)2NiMnO6 thin films
Authors: Langenberg E. , Fina I. , Gemeiner P. , Dkhil B. , Fàbrega L. , Varela M. , Fontcuberta J.
Published: January 2012

We report here temperature-dependent x-ray structural and Raman spectroscopy data, on the ferromagnetic double-perovskite (Bi0.9La0.1)2NiMnO6 epitaxial thin films. Results indicate a ferroelectric transition occurring at about 450 °C. Low-temperature polarization loops allow to clearly observing polarization switching, thus confirming the multiferroic character of this oxide, and indicate a lower bound of about 6 μC/cm2.
Direct simulation Monte Carlo method for an arbitrary intermolecular potential
Authors: Sharipov Felix , Strapasson José L.
Published: January 2012

A scheme to implement an arbitrary intermolecular potential into the direct simulation Monte Carlo method is proposed. To illustrate the scheme, two benchmark problems are solved employing the Lennard-Jones potential. Since the computational effort of the new scheme is comparable with that of the hard sphere model of molecules, it can completely substitute the widely used models such as variable hard spheres and variable soft spheres.
Will genetics offer a permanent solution to breech strike?
Authors: Richards J. S. , Atkins K. D.
Published: January 2012

There are several options for managing flystrike other than mulesing. Breeding for plainer animals that do not require mulesing is an attractive, permanent long-term solution. Breech wrinkle is the key predisposing factor for breech and tail strike. Little effort has been made to reduce wrinkle score in sheep because mulesing was so successful and because there is a perception that reducing wrinkle score will reduce fleece weight. Fleece weight will be reduced if single-trait selection for wrinkle is applied, but if breech wrinkle is included in an index, the negative effect of wrinkle on other production traits can be minimised using the same method as that used to accommodate the negative correlation between fibre diameter and fleece weight. Breeding programs for reduced breech wrinkle should be used in combination with short-term tactical management strategies, especially during the initial stages of the breeding program. The need for tactical management will decrease as the program progresses. This approach can be applied using information that can be recorded easily and at low cost.
Structuring economic incentives to reduce emissions from deforestation within Indonesia
Authors: Busch Jonah , Lubowski Ruben N. , Godoy Fabiano , Steininger Marc , Yusuf Arief A. , Austin Kemen , Hewson Jenny , Juhn Daniel , Farid Muhammad , Boltz Frederick
Published: January 2012

We estimate and map the impacts that alternative national and subnational economic incentive structures for reducing emissions from deforestation (REDD+) in Indonesia would have had on greenhouse gas emissions and national and local revenue if they had been in place from 2000 to 2005. The impact of carbon payments on deforestation is calibrated econometrically from the pattern of observed deforestation and spatial variation in the benefits and costs of converting land to agriculture over that time period. We estimate that at an international carbon price of $10/tCO
2
e, a “mandatory incentive structure,” such as a cap-and-trade or symmetric tax-and-subsidy program, would have reduced emissions by 163–247 MtCO
2
e/y (20–31% below the without-REDD+ reference scenario), while generating a programmatic budget surplus. In contrast, a “basic voluntary incentive structure” modeled after a standard payment-for-environmental-services program would have reduced emissions nationally by only 45–76 MtCO
2
e/y (6–9%), while generating a programmatic budget shortfall. By making four policy improvements—paying for net emission reductions at the scale of an entire district rather than site-by-site; paying for reductions relative to reference levels that match business-as-usual levels; sharing a portion of district-level revenues with the national government; and sharing a portion of the national government's responsibility for costs with districts—an “improved voluntary incentive structure” would have been nearly as effective as a mandatory incentive structure, reducing emissions by 136–207 MtCO
2
e/y (17–26%) and generating a programmatic budget surplus.
Divergence of duplicate genes in exon–intron structure
Authors: Xu Guixia , Guo Chunce , Shan Hongyan , Kong Hongzhi
Published: January 2012

Gene duplication plays key roles in organismal evolution. Duplicate genes, if they survive, tend to diverge in regulatory and coding regions. Divergences in coding regions, especially those that can change the function of the gene, can be caused by amino acid-altering substitutions and/or alterations in exon–intron structure. Much has been learned about the mode, tempo, and consequences of nucleotide substitutions, yet relatively little is known about structural divergences. In this study, by analyzing 612 pairs of sibling paralogs from seven representative gene families and 300 pairs of one-to-one orthologs from different species, we investigated the occurrence and relative importance of structural divergences during the evolution of duplicate and nonduplicate genes. We found that structural divergences have been very prevalent in duplicate genes and, in many cases, have led to the generation of functionally distinct paralogs. Comparisons of the genomic sequences of these genes further indicated that the differences in exon–intron structure were actually accomplished by three main types of mechanisms (exon/intron gain/loss, exonization/pseudoexonization, and insertion/deletion), each of which contributed differently to structural divergence. Like nucleotide substitutions, insertion/deletion and exonization/pseudoexonization occurred more or less randomly, with the number of observable mutational events per gene pair being largely proportional to evolutionary time. Notably, however, compared with paralogs with similar evolutionary times, orthologs have accumulated significantly fewer structural changes, whereas the amounts of amino acid replacements accumulated did not show clear differences. This finding suggests that structural divergences have played a more important role during the evolution of duplicate than nonduplicate genes.
An
rhs
gene of
Pseudomonas aeruginosa
encodes a virulence protein that activates the inflammasome
Authors: Kung Vanderlene L. , Khare Sonal , Stehlik Christian , Bacon Elizabeth M. , Hughes Ami J. , Hauser Alan R.
Published: January 2012

The
rhs
genes are a family of enigmatic composite genes, widespread among Gram-negative bacteria. In this study, we characterized
rhsT
, a
Pseudomonas aeruginosa rhs
gene that encodes a toxic protein. Expression of
rhsT
was induced upon contact with phagocytic cells. The RhsT protein was exposed on the bacterial surface and translocated into phagocytic cells; these cells subsequently underwent inflammasome-mediated death. Moreover, RhsT enhanced host secretion of the potent proinflammatory cytokines IL-1β and IL-18 in an inflammasome-dependent manner. In a mouse model of acute pneumonia, infection with a
P. aeruginosa
strain lacking
rhsT
was associated with less IL-18 production, fewer recruited leukocytes, reduced pulmonary bacterial load, and enhanced animal survival. Thus,
rhsT
encodes a virulence determinant that activates the inflammasome.
A morphologically specialized soldier caste improves colony defense in a neotropical eusocial bee
Authors: Grüter Christoph , Menezes Cristiano , Imperatriz-Fonseca Vera L. , Ratnieks Francis L. W.
Published: January 2012

Division of labor among workers is common in insect societies and is thought to be important in their ecological success. In most species, division of labor is based on age (temporal castes), but workers in some ants and termites show morphological specialization for particular tasks (physical castes). Large-headed soldier ants and termites are well-known examples of this specialization. However, until now there has been no equivalent example of physical worker subcastes in social bees or wasps. Here we provide evidence for a physical soldier subcaste in a bee. In the neotropical stingless beeTetragonisca angustula, nest defense is performed by two groups of guards, one hovering near the nest entrance and the other standing on the wax entrance tube. We show that both types of guards are 30% heavier than foragers and of different shape; foragers have relatively larger heads, whereas guards have larger legs. Low variation within each subcaste results in negligible size overlap between guards and foragers, further indicating that they are distinct physical castes. In addition, workers that remove garbage from the nest are of intermediate size, suggesting that they might represent another unrecognized caste. Guards or soldiers are reared in low but sufficient numbers (1–2% of emerging workers), considering that <1% usually perform this task. When challenged by the obligate robber beeLestrimelitta limao, an important natural enemy, larger workers were able to fight for longer before being defeated by the much larger robber. This discovery opens up opportunities for the comparative study of physical castes in social insects, including the question of why soldiers appear to be so much rarer in bees than in ants or termites.
β3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons
Authors: Pozo Karine , Cingolani Lorenzo A. , Bassani Silvia , Laurent Fanny , Passafaro Maria , Goda Yukiko
Published: January 2012

The integrins are transmembrane receptors for ECM proteins, and they regulate various cellular functions in the central nervous system. In hippocampal neurons, the β3 integrin subtype is required for homeostatic synaptic scaling of AMPA receptors (AMPARs) induced by chronic activity deprivation. The surface level of β3 integrin in postsynaptic neurons directly correlates with synaptic strength and the abundance of synaptic GluA2 AMPAR subunit. Although these observations suggest a functional link between β3 integrin and AMPAR, little is known about the mechanistic basis for the connection. Here we investigate the nature of β3 integrin and AMPAR interaction underlying the β3 integrin-dependent control of synaptic AMPAR expression and thus synaptic strength. We show that β3 integrin and GluA2 subunit form a complex in mouse brain that involves the direct binding between their cytoplasmic domains. In contrast, β3 integrin associates with GluA1 AMPAR subunit only weakly, and, in a heterologous expression system, the interaction requires the coexpression of GluA2. Surprisingly, in hippocampal pyramidal neurons, expressing β3 integrin mutants with either increased or decreased affinity for extracellular ligands has no differential effects in elevating excitatory synaptic currents and surface GluA2 levels compared with WT β3 integrin. Our findings identify an integrin family member, β3, as a direct interactor of an AMPAR subunit and provide molecular insights into how this cell-adhesion protein regulates the composition of cell-surface AMPARs.
How
Staphylococcus aureus
biofilms develop their characteristic structure
Authors: Periasamy Saravanan , Joo Hwang-Soo , Duong Anthony C. , Bach Thanh-Huy L. , Tan Vee Y. , Chatterjee Som S. , Cheung Gordon Y. C. , Otto Michael
Published: January 2012

Biofilms cause significant problems in the environment and during the treatment of infections. However, the molecular mechanisms underlying biofilm formation are poorly understood. There is a particular lack of knowledge about biofilm maturation processes, such as biofilm structuring and detachment, which are deemed crucial for the maintenance of biofilm viability and the dissemination of cells from a biofilm. Here, we identify the phenol-soluble modulin (PSM) surfactant peptides as key biofilm structuring factors in the premier biofilm-forming pathogen
Staphylococcus aureus
. We provide evidence that all known PSM classes participate in structuring and detachment processes. Specifically, absence of PSMs in isogenic
S. aureus psm
deletion mutants led to strongly impaired formation of biofilm channels, abolishment of the characteristic waves of biofilm detachment and regrowth, and loss of control of biofilm expansion. In contrast, induced expression of
psm
loci in preformed biofilms promoted those processes. Furthermore, PSMs facilitated dissemination from an infected catheter in a mouse model of biofilm-associated infection. Moreover, formation of the biofilm structure was linked to strongly variable, quorum sensing-controlled PSM expression in biofilm microenvironments, whereas overall PSM production remained constant to ascertain biofilm homeostasis. Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease.
Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodes
Authors: Shiroguchi Katsuyuki , Jia Tony Z. , Sims Peter A. , Xie X. Sunney
Published: January 2012

RNA sequencing (RNA-Seq) is a powerful tool for transcriptome profiling, but is hampered by sequence-dependent bias and inaccuracy at low copy numbers intrinsic to exponential PCR amplification. We developed a simple strategy for mitigating these complications, allowing truly digital RNA-Seq. Following reverse transcription, a large set of barcode sequences is added in excess, and nearly every cDNA molecule is uniquely labeled by random attachment of barcode sequences to both ends. After PCR, we applied paired-end deep sequencing to read the two barcodes and cDNA sequences. Rather than counting the number of reads, RNA abundance is measured based on the number of unique barcode sequences observed for a given cDNA sequence. We optimized the barcodes to be unambiguously identifiable, even in the presence of multiple sequencing errors. This method allows counting with single-copy resolution despite sequence-dependent bias and PCR-amplification noise, and is analogous to digital PCR but amendable to quantifying a whole transcriptome. We demonstrated transcriptome profiling of
Escherichia coli
with more accurate and reproducible quantification than conventional RNA-Seq.
Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon
Authors: Rivollier Aymeric , He Jianping , Kole Abhisake , Valatas Vassilis , Kelsall Brian L.
Published: January 2012

Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hiCX3CR1hi (CD11b+CD103−) cells account for 80% of mouse colonic lamina propria MHC-IIhi cells. Both CD11c+ and CD11c− cells within this population were identified as MPs based on multiple criteria, including an MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1−CD11b− DCs, CD103+CX3CR1−CD11b+ DCs, and CD103−CX3CR1intCD11b+ DCs. In noninflammatory conditions, Ly6Chi monocytes (MOs) differentiated primarily into CD11c+ but not CD11c− MPs. In contrast, during colitis, Ly6Chi MOs massively invaded the colon and differentiated into proinflammatory CD103−CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS, and TNF. These findings demonstrate the dual capacity of Ly6Chi blood MOs to differentiate into either regulatory MPs or inflammatory DCs in the colon and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions.
Induction of antisporozoite antibodies by biting of transgenic Anopheles stephensi delivering malarial antigen via blood feeding
Authors: Yamamoto D. S. , Sumitani M. , Nagumo H. , Yoshida S. , Matsuoka H.
Published: January 2012

We produced a transgenic mosquito expressing a rodent malaria vaccine candidate antigen in the salivary gland. Three tandemly repeated amino acid units from the repeat region of circumsporozoite protein of Plasmodium berghei (PbCS3R) fused to red fluorescent protein (monomeric DsRed) was chosen as a vaccine candidate antigen. Immunoblot and fluorescence microscopic analyses showed the transgene expression in the female salivary gland. The transgene product was released from the proboscis as a component of saliva. The monomeric DsRed‐fusion expression system could be suitable for transgene secretion in the saliva of female mosquitoes. Mice repeatedly bitten by transgenic mosquitoes raised antibodies against P. berghei sporozoites, and the sera had protective ability against sporozoite invasion of human hepatoma HepG2 cells. These results suggest that transgene products are immunogenically active in saliva, and induce the antibodies to malaria parasite. These findings indicate that this technology has the potential for production of a ‘flying vaccinator’ for rodent malaria parasites.
BsrG/SR4 from Bacillus subtilis– the first temperature‐dependent type I toxin–antitoxin system
Authors: Jahn Natalie , Preis Heike , Wiedemann Christoph , Brantl Sabine
Published: January 2012

Here, we describe bsrG/SR4, a novel type I toxin–antitoxin system from the SPβ prophage region of the Bacillus subtilis chromosome. The 294‐nucleotide bsrG RNA encodes a 38‐amino‐acid toxin, whereas SR4 is a 180‐nucleotide antisense RNA that acts as the antitoxin. Both genes overlap by 123 nucleotides. BsrG expression increases at the onset of stationary phase. The sr4 promoter is 6‐ to 10‐fold stronger than the bsrG promoter. Deletion of sr4 stabilizes bsrG mRNA and causes cell lysis on agar plates, which is due to the BsrG peptide and not the bsrG mRNA. SR4 overexpression could compensate cell lysis caused by overexpression of bsrG. SR4 interacts with the 3′ UTR of bsrG RNA, thereby promoting its degradation. RNase III cleaves the bsrG RNA/SR4 duplex at position 185 of bsrG RNA, but is not essential for the function of the toxin–antitoxin system. Endoribonuclease Y and 3′‐5′ exoribonuclease R participate in the degradation of both bsrG RNA and SR4, whereas PnpA processes three SR4 precursors to the mature RNA. A heat shock at 48°C results in faster degradation and, therefore, significantly decreased amounts of bsrG RNA.
Notch Signalling Regulates Cytokine Production by CD8+ and CD4+ T Cells
Authors: Sauma D. , Ramirez A. , Alvarez K. , Rosemblatt M. , Bono M. R.
Published: January 2012

The Notch signalling pathway regulates several aspects of cellular differentiation such as T lineage commitment and effector functions on peripheral T cells; however, there is limited information regarding Notch receptor expression on different T cell subsets and the putative role of the different receptors on T cell effector function. Here, we studied the protein expression of Notch receptors on murine T cells in vitro and in vivo and analysed the role of the Notch pathway in cytokine production by CD4+ and CD8+ T cells. We found that resting CD4+ and CD8+ T cells do not express Notch receptors, but they upregulate Notch 1 and Notch 2 shortly after in vitro and in vivo activation. Using a γ‐secretase inhibitor, which blocks Notch signalling through all Notch receptors, we demonstrated that the Notch pathway regulates IL‐10 production by CD4+ T cells and IFN‐γ and IL‐17 production by CD8+ T cells. These results suggest that Notch 1 and 2 are expressed by CD4+ and CD8+ T cells and represent the putative Notch receptors that regulate effector functions and cytokine production by these cells.
Partial Tolerance Induced by Transplantation of Spatially Separated Thymuses: A Cue for T Cell Retolerization in Thymus Grafts
Authors: Zhou J. , Wang X. , Luo G. , He W. , Cui Y. , Tan J. , Yang S. , Yang J. , Sun W. , Song H. , Xiang F. , Yao Z. , Liu D. , Wu Y. , Wu J.
Published: January 2012

Thymus grafts made up of mixed syngeneic and xenogeneic thymus tissues could induce donor‐specific tolerance to xenografts with no development of autoimmune syndrome (AIS). But the requirements for the simultaneous presentation of tissue antigens from both species in the process of T cell development in thymus grafts have not hitherto been defined. To do this, we setup a model in which xenothymus grafts from F344 rats were heterotopically implanted into BALB/c nude mice carrying syngeneic thymus grafts, and the grafts were either mixed together or spatially separately; next, we examined the induction of donor‐specific tolerance, any pathological changes and the distribution of T lymphocytes. In contrast to the mixed thymus grafts, spatially separated thymus transplants could neither induce a long‐term tolerance to skin grafts nor prevent AIS completely. 51Cr‐labelled cell‐tracing experiments showed that mature peripheral T cells could re‐enter into both kinds of thymus grafts, while the T cells isolated from the syngeneic thymus tended to concentrate in the xenothymus grafts. Hence, our data suggest that the immune tolerance induced by mixed thymus transplants could be partially reversed if the thymus tissues from donors and recipients were segregated by spatial telorism. The uneven recirculation of mature T cells might imply that T cells get retolerized within the thymus grafts.
Enveloped Virus but not Bacteria Block IL‐13 Responses in Human Cord Blood T Cells In Vitro
Authors: Svensson A. , Nordström I. , Rudin A. , Bergström T. , Eriksson K.
Published: January 2012

Infections that occur early in life may have a beneficial effect on the immune system and thereby reduce the risk of allergen sensitization and/or allergic disease. It is not yet clear to what extent specific virus and/or bacteria can mediate this effect. The purpose of this study was to assess the role of virus and bacteria in CD4+ T cell‐derived cytokine production in newborns. We compared the effects of five bacteria (Staphlococcus aureus, Escherichia coli, Clostridium difficile, Lactobacillus rhamnosus and Bifidobacterium bifidus) and seven virus (adenovirus, coronavirus, cytomegalovirus, herpes simplex virus, influenza virus, morbillivirus and poliovirus) on the Th1/Th2 cytokine production in mixed lymphocyte reactions using CD4+ T cells from cord blood cocultured with allogenic myeloid or plasmacytoid dendritic cells. When comparing the baseline cytokine production prior to microbial stimulation, we observed that cord plasmacytoid DC were stronger inducers of Th2 cytokines (IL‐5 and IL‐13) compared with cord myeloid DC and to adult DC. When adding microbes to these cultures, bacteria and virus differed in two major respects; Firstly, all enveloped viruses, but none of the bacteria, blocked Th2 (IL‐13) production by cord CD4+ cells. Secondly, all Gram‐positive bacteria, but none of the virus, induced IL‐12p40 responses, but the IL‐12p40 responses did not affect Th1 cytokine production (IFN‐γ). Instead, Th1 responses were correlated with the capacity to induce IFN‐α secretion, which in cord cells were induced by S. aureus and influenza virus alone. These data imply that enveloped virus can deviate Th2 responses in human cord T cells.
Advances in Proteomics of Mycobacterium leprae
Authors: Parkash O. , Singh B. P.
Published: January 2012

Although Mycobacterium leprae was the first bacterial pathogen identified causing human disease, it remains one of the few that is non‐cultivable. Understanding the biology of M. leprae is one of the primary challenges in current leprosy research. Genomics has been extremely valuable, nonetheless, functional proteins are ultimately responsible for controlling most aspects of cellular functions, which in turn could facilitate parasitizing the host. Furthermore, bacterial proteins provide targets for most of the vaccines and immunodiagnostic tools. Better understanding of the proteomics of M. leprae could also help in developing new drugs against M. leprae. During the past nearly 15 years, there have been several developments towards the identification of M. leprae proteins employing contemporary proteomics tools. In this review, we discuss the knowledge gained on the biology and pathogenesis of M. leprae from current proteomic studies.