bluuebunny/crossref_metadata_2025 huggingface dataset:
Disturbance intensity and seasonality affect the resprouting ability of the neotropical dry-forest tree Acacia pennatula: do resources stored below-ground matter?
Authors: Peguero Guille , Espelta Josep Maria
Published: August 2011

Many plant species in tropical dry forests partly base their ability to persist after disturbance on resprouting. Yet little is known if this ability can be affected by the intensity and seasonality of disturbance and whether the amount of resources (starch, N, P) stored in the taproot may constrain this response. We investigated resprouting after experimental clipping or burning, applied before or after the dry season and repeatedly in Acacia pennatula individuals in wooded rangelands of North-West Nicaragua. Each treatment was applied to 12 trees and replicated in six plots. One year after the onset of the experiment, survival and biomass recovery were significantly lower in burned than in clipped individuals (78% ± 4% and 75.3 ± 8.0 g vs. 94% ± 2% and 79.1 ± 6.8 g; mean ± SE). Whatever the disturbance applied, trees disturbed after the dry season significantly showed the lowest survival, growth and concentration of N and P. These results suggest that resprouting in dry tropical species may be constrained by intense disturbances (e.g. burning) but especially if they occur towards the end of the dry season. This phenological constraint could be due to the reduced availability of N and P as this dry season progresses.
Do roads lead to grassland degradation or restoration? A case study in Inner Mongolia, China
Authors: Deng Xiangzheng , Huang Jikun , Huang Qiuqiong , Rozelle Scott , Gibson John
Published: August 2011

We use satellite remote sensing data of grassland cover in Inner Mongolia, China to test whether the existence of and the size of roads in 1995 is associated with the nature of the grassland in 2000 and/or if it affects the rate of change of the grassland between 1995 and 2000. The regression results show that the impact of roads on grassland cover depends on the nature of the resource. When the grassland is composed of relatively high quality grassland, roads lead to degradation, whereas when grassland resources are sparse, access to a road results in the restoration of the resource.
Estimating the value of the reduction in air pollution during the Beijing Olympics
Authors: Du Xiaoyan , Mendelsohn Robert O.
Published: August 2011

This study estimates the willingness-to-pay (WTP) of Beijing residents in order to maintain the improved air quality experienced during the Olympic Games. A double-bounded contingent valuation method is applied to a survey of 566 Beijing residents. The results indicate that the mean annual WTP per household is between CNY 22,000 and 24,000, and the median WTP is around CNY 1,700. The WTP for this actually experienced improvement is significantly higher than the results from previous hypothetical WTP surveys in China.
Is retrieval-induced forgetting behind the bilingual disadvantage in word production?
Authors: RUNNQVIST ELIN , COSTA ALBERT
Published: August 2011

Levy, Mc Veigh, Marful and Andreson (2007) found that naming pictures in L2 impaired subsequent recall of the L1 translation words. This was interpreted as evidence for a domain-general inhibitory mechanism (RIF) underlying first language attrition. Because this result is at odds with some previous findings and theoretical assumptions, we wanted to assess its reliability and replicate the experiment with various groups. Participants were first shown drawings along with their labels in the non-dominant language. Afterwards, they named 75% of these drawings in their first language or in their non-dominant language. Finally, participants’ memory of all L1 words was tested through the presentation of a rhyme-cue. Recall of L1 words was better after naming pictures in the non-dominant language compared to when the picture was not named at all. This result suggests that speaking a second language protects rather than harms the memory of our first language.
Socio-economic status and urbanization are linked to snacks and obesity in adolescents in Botswana
Authors: Maruapula Segametsi D , Jackson Jose C , Holsten Joanna , Shaibu Sheila , Malete Leapetswe , Wrotniak Brian , Ratcliffe Sarah J , Mokone George G , Stettler Nicolas , Compher Charlene
Published: August 2011

Objective

To describe patterns of food consumption associated with overweight/ obesity (OW/OB) and their links to socio-economic status (SES) and urbanization.

Design

A nationwide cross-sectional survey.

Setting

Secondary schools in cities, towns and villages in Botswana, Africa.

Subjects

A total of 746 adolescent schoolchildren.

Results

OW/OB is associated with greater SES, city residence and a snack-food diet pattern. Students belonging to higher SES compared with those from a lower SES background reported significantly (P< 0·01) more daily servings of snack foods (1·55v. 0·76) and fewer servings of traditional diet foods (0·99v. 1·68) and also reported that they ate meals outside the home more often (90 %v. 72 %). Students in cities ate significantly (P< 0·01) more servings of snacks (1·69v. 1·05v. 0·51) and fewer servings of traditional foods (0·67v. 1·52v. 1·61) compared with those in urban and rural villages. The odds of OW/OB were increased 1·16-fold with a snack-food diet, a result that was diminished when controlled for SES.

Conclusions

These data suggest that nutritional transition occurs at different rates across urbanization and SES levels in Botswana. In cities, increasing the availability of fruit while reducing access to or portion sizes of snack items is important. Emphasis on continued intake of traditional foods may also be helpful as rural areas undergo economic and infrastructural development.
Nutritional knowledge in European adolescents: results from the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study
Authors: Sichert-Hellert Wolfgang , Beghin Laurent , De Henauw Stefaan , Grammatikaki Evangelia , Hallström Lena , Manios Yannis , Mesana María I , Molnár Dénes , Dietrich Sabine , Piccinelli Raffaela , Plada Maria , Sjöström Michael , Moreno Luis A , Kersting Mathilde
Published: August 2011

Objective

To build up sufficient knowledge of a ‘healthy diet’. Here, we report on the assessment of nutritional knowledge using a uniform method in a large sample of adolescents across Europe.

Design

A cross-sectional study.

Setting

The European multicentre HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study conducted in 2006–2007 in ten cities in Austria, Belgium, France, Germany, Greece (one inland and one island city), Hungary, Italy, Spain and Sweden.

Subjects

A total of 3546 adolescents (aged 12·5–17·5 years) completed a validated nutritional knowledge test (NKT). Socio-economic variables and anthropometric data were considered as potential confounders.

Results

NKT scores increased with age and girls had higher scores compared with boys (62 % v. 59 %; P < 0·0001). Scores were approximately 10 % lower in ‘immigrant’ adolescents or in adolescents with ‘immigrant’ mothers. Misconceptions with respect to the sugar content in food or in beverages were found. Overall, there was no correlation between BMI values and NKT scores. After categorization according to BMI, scores increased significantly with BMI group only in boys. These differences disappeared after controlling for socio-economic status (SES). Smoking status and educational level of the mother influenced the NKT scores significantly in boys, as well as the educational levels of both parents in girls.

Conclusions

Nutritional knowledge was modest in our sample. Interventions should be focused on the lower SES segments of the population. They should be initiated at a younger age and should be combined with environmental prevention (e.g. healthy meals in school canteens).
IRREDUCIBLE REPRESENTATIONS OF THE HAMILTONIAN ALGEBRAH(2r;n)
Authors: YAO YU-FENG , SHU BIN
Published: August 2011

LetL=H(2r;n) be a graded Lie algebra of Hamiltonian type in the Cartan type series over an algebraically closed field of characteristicp>2. In the generalized restricted Lie algebra setup, any irreducible representation ofLcorresponds uniquely to a (generalized)p-characterχ. When the height ofχis no more than min {pni−pni−1∣i=1,2,…,2r}−2, the corresponding irreducible representations are proved to be induced from irreducible representations of the distinguished maximal subalgebraL0with the aid of an analogy of Skryabin’s category ℭ for the generalized Jacobson–Witt algebras and modulo finitely many exceptional cases. Since the exceptional simple modules have been classified, we can then give a full description of the irreducible representations withp-characters of height below this number.
Periodic structures in the equatorial ionosphere
Authors: Huang Cheryl Y. , Delay Susan H. , Roddy Patrick A. , Sutton Eric K.
Published: August 2011

The plasma densities detected by the Planar Langmuir Probe (PLP) on board the Communication/Navigation Outage Forecasting System (C/NOFS) satellite have been analyzed for the June 2008 period. This interval, which corresponds to one of the quietest periods in the space era, exhibited broad plasma decreases (BPDs) which we have reported previously. In order to treat the data quantitatively, we have detrended the PLP data by using the International Reference Ionosphere model to remove variations in density due to changes in spacecraft altitude and latitude along the orbit. In this paper we present results of a statistical analysis of C/NOFS detrended plasma densities during June 2008 as well as neutral densities from the Gravity Recovery and Climate Experiment measured during the same period. The results show periodic structures in both charged and neutral species, most evident in limited local times. These structures resemble wave‐4 nonmigrating tides. BPDs persist in the detrended data and appear as one of the minima in the periodic signatures, most strikingly on the nightside.
Gaussian setting time for solute transport in fluvial systems
Authors: Zhang Yong , Meerschaert Mark M.
Published: August 2011

Gaussian setting time is the time scale at which solute plumes converge to their asymptotic Gaussian shape. This study estimates the Gaussian setting time using a high‐resolution hydrofacies model of a typical fluvial system, with an instantaneous point source in the mobile phase. Monte Carlo simulations are augmented by a time‐nonlocal transport model to forecast plume shape at late time. Analysis of plume spatial moments indicates that convergence to Fickian transport is affected by molecular diffusion and the thickness of low‐permeability floodplain layers. These layers can cause non‐Gaussian tailing to persist at late time because the low‐permeability lenses are elongated in the horizontal, so that most particles escape vertically by diffusion. A simple empirical setting time formula is developed, which can be fitted using data from driller's logs that characterize the thickness of the low‐permeability lenses. The empirical formula may be useful for predicting setting time in fluvial aquifers similar to those considered in this study. For such aquifers, the plume will often exit the region prior to the setting time, so the asymptotic Gaussian model will not be a useful predictor of plume shape.
Cratering asymmetry on the Moon: New insight from the Apollo Passive Seismic Experiment
Authors: Kawamura Taichi , Morota Tomokatsu , Kobayashi Naoki , Tanaka Satoshi
Published: August 2011

The synchronous rotation of the Moon can lead to an asymmetry in the cratering rate between the leading and trailing sides of lunar orbital motion. The observation of the Apollo Passive Seismic Experiment can be viewed as a continuous seismic observation of lunar impacts; it provides information of the current bombardments and small impact events of meter‐sized craters. To evaluate the current leading‐trailing cratering asymmetry on the Moon, we investigated the spatial distribution of impact sites determined by Apollo seismic observation. We determined that the number density of impacts on the leading side is substantially higher than that on the trailing side. In addition, we discovered a possible enhancement of the number density of 1.4 ± 0.4 to 1.9 ± 0.5 on the leading side relative to that of the trailing side. This indicated that the cratering asymmetry predicted from historical cratering records also exists in the current low‐magnitude impacts.
Hyporheic exchange due to channel‐spanning logs
Authors: Sawyer Audrey H. , Bayani Cardenas M. , Buttles Jim
Published: August 2011

The flow of river water around large woody debris (LWD) creates pressure gradients along the riverbed that drive a large zone of river‐groundwater mixing, or hyporheic exchange. Flume experiments and numerical simulations show that river water downwells into the riverbed upstream of a channel‐spanning log and upwells downstream. Exchange rates are greatest near the log and decay exponentially with distance upstream and downstream. We developed equations for bed pressure profiles and hyporheic exchange rates in the vicinity of a channel‐spanning log that can be used to evaluate the impact of LWD removal or reintroduction on hyporheic mixing. The magnitude of pressure disturbance along the bed (and thus hyporheic exchange) increases with the fraction of channel depth blocked by the log and channel Froude number. Exchange rates are relatively insensitive to relative depth of the log (gap ratio). At natural densities, LWD in lowland streams drives reach‐averaged hyporheic exchange rates similar to a ripple‐covered bed. However, the length scales and residence times of hyporheic exchange due to LWD are greater. By removing LWD from streams, humans have altered patterns and rates of hyporheic exchange, which influence habitat distribution and quality for invertebrates and fish.
mTORC2 targets AGC kinases through Sin1-dependent recruitment
Authors: Cameron Angus J. M. , Linch Mark D. , Saurin Adrian T. , Escribano Cristina , Parker Peter J.
Published: August 2011

The protein kinase TOR (target of rapamycin) is a key regulator of cell growth and metabolism with significant clinical relevance. In mammals, TOR signals through two distinct multi-protein complexes, mTORC1 and mTORC2 (mammalian TOR complex 1 and 2 respectively), the subunits of which appear to define the operational pathways. Rapamycin selectively targets mTORC1 function, and the emergence of specific ATP-competitive kinase inhibitors has enabled assessment of dual mTORC1 and mTORC2 blockade. Little is known, however, of the molecular action of mTORC2 components or the relative importance of targeting this pathway. In the present study, we have identified the mTORC2 subunit Sin1 as a direct binding partner of the PKC (protein kinase C) ϵ kinase domain and map the interaction to the central highly conserved region of Sin1. Exploiting the conformational dependence for PKC phosphorylation, we demonstrate that mTORC2 is essential for acute priming of PKC. Inducible expression of Sin1 mutants, lacking the PKC-interaction domain, displaces endogenous Sin1 from mTORC2 and disrupts PKC phosphorylation. PKB (protein kinase B)/Akt phosphorylation is also suppressed by these Sin1 mutants, but not the mTORC1 substrate p70S6K (S6 kinase), providing evidence that Sin1 serves as a selectivity adaptor for the recruitment of mTORC2 targets. This inducible selective mTORC2 intervention is used to demonstrate a key role for mTORC2 in cell proliferation in three-dimensional culture.
The Sisters of the Golden Section
Authors: Navon David
Published: August 2011

The golden proportion is widely believed to be extraordinarily prevalent in nature and the arts, which is often ascribed to it being the limit of the ratio between any two successive elements in the Fibonacci sequence. It is suggested here that the golden ratio may not be as exceptional as generally believed. Mathematically, some interesting properties are common to all members of a family of sequences, denoted ARS, characterised as solutions to the classic rabbit reproduction problem varying on some parameter, j, including the Fibonacci sequence as a proto-typical member—ARS2. Furthermore, for j > 1, any limit of the ratio between successive elements in ARS j, shares the same formal properties with all other such limits. Three actual interpretations and three further geometric applications of ARS3, all intimately analogous to corresponding ARS2 ones, are presented for the sake of illustration. Empirically, it is suggested here that, owing to the communality of interesting mathematical properties between ARS sequences, as well as between corresponding limits, nature might appear to have made use of some other limits, aside of its variegated use of the limit of ARS2 — the golden ratio. Initial empirical clues are provided. Finally, the issue whether there really is special import to golden proportions in nature and the arts is revisited in view of some empirical comparisons of appearances related to Fibonacci numbers and ARS3 numbers, particular its limit (∼1.466) and the inverse of that limit (∼0:682). It is argued that the claim that Fibonacci-related numbers are especially distinguished seems to warrant a more qualified approach than it has often met.
Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)
Authors: Samways Damien S. K. , Khakh Baljit S. , Dutertre Sébastien , Egan Terrance M.
Published: August 2011

P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathways within the extracellular domain. One of these is the central pathway spanning the entire length of the extracellular domain and covering a distance of ≈70 Å. The second consists of three lateral portals, adjacent to the membrane and connected to the transmembrane pore by short tunnels. Here, we demonstrate the preferential use of the lateral portals. Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion's diffusive path before it succumbs to transmembrane electrochemical gradients.
Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome
Authors: Kim Kun-Yong , Hysolli Eriona , Park In-Hyun
Published: August 2011

Rett syndrome (RTT) is one of the most prevalent female neurodevelopmental disorders that cause severe mental retardation. Mutations in methyl CpG binding protein 2 (MeCP2) are mainly responsible for RTT. Patients with classical RTT exhibit normal development until age 6–18 mo, at which point they become symptomatic and display loss of language and motor skills, purposeful hand movements, and normal head growth. Murine genetic models and postmortem human brains have been used to study the disease and enable the molecular dissection of RTT. In this work, we applied a recently developed reprogramming approach to generate a novel in vitro human RTT model. Induced pluripotent stem cells (iPSCs) were derived from RTT fibroblasts by overexpressing the reprogramming factors OCT4, SOX2, KLF4, and MYC. Intriguingly, whereas some iPSCs maintained X chromosome inactivation, in others the X chromosome was reactivated. Thus, iPSCs were isolated that retained a single active X chromosome expressing either mutant or WT MeCP2, as well as iPSCs with reactivated X chromosomes expressing both mutant and WT MeCP2. When these cells underwent neuronal differentiation, the mutant monoallelic or biallelelic RTT-iPSCs displayed a defect in neuronal maturation consistent with RTT phenotypes. Our in vitro model of RTT is an important tool allowing the further investigation of the pathophysiology of RTT and the development of the curative therapeutics.
Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in
Drosophila
Authors: Lee Pei-Tseng , Lin Hsuan-Wen , Chang Yu-Hsuan , Fu Tsai-Feng , Dubnau Josh , Hirsh Jay , Lee Tzumin , Chiang Ann-Shyn
Published: August 2011

Pavlovian olfactory learning in
Drosophila
produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the
amnesiac
gene, and anesthesia-resistant memory (ARM), which requires the
radish
gene. Here, we report that ARM is specifically enhanced or inhibited in flies with elevated or reduced serotonin (5HT) levels, respectively. The requirement for 5HT was additive with the memory defect of the
amnesiac
mutation but was occluded by the
radish
mutation. This result suggests that 5HT and Radish protein act on the same pathway for ARM formation. Three supporting lines of evidence indicate that ARM formation requires 5HT released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in
Drosophila
: (
i
) DPM neurons were 5HT-antibody immunopositive; (
ii
) temporal inhibition of 5HT synthesis or release from DPM neurons, but not from other serotonergic neurons, impaired ARM formation; (
iii
) knocking down the expression of d5HT1A serotonin receptors in α/β MB neurons, which are innervated by DPM neurons, inhibited ARM formation. Thus, in addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, the two DPM neurons also release 5HT acting on MB neurons for ARM formation.
Multialternative drift-diffusion model predicts the relationship between visual fixations and choice in value-based decisions
Authors: Krajbich Ian , Rangel Antonio
Published: August 2011

How do we make decisions when confronted with several alternatives (e.g., on a supermarket shelf)? Previous work has shown that accumulator models, such as the drift-diffusion model, can provide accurate descriptions of the psychometric data for binary value-based choices, and that the choice process is guided by visual attention. However, the computational processes used to make choices in more complicated situations involving three or more options are unknown. We propose a model of trinary value-based choice that generalizes what is known about binary choice, and test it using an eye-tracking experiment. We find that the model provides a quantitatively accurate description of the relationship between choice, reaction time, and visual fixation data using the same parameters that were estimated in previous work on binary choice. Our findings suggest that the brain uses similar computational processes to make binary and trinary choices.
grassy tillers1
promotes apical dominance in maize and responds to shade signals in the grasses
Authors: Whipple Clinton J. , Kebrom Tesfamichael H. , Weber Allison L. , Yang Fang , Hall Darren , Meeley Robert , Schmidt Robert , Doebley John , Brutnell Thomas P. , Jackson David P.
Published: August 2011

The shape of a plant is largely determined by regulation of lateral branching. Branching architecture can vary widely in response to both genotype and environment, suggesting regulation by a complex interaction of autonomous genetic factors and external signals. Tillers, branches initiated at the base of grass plants, are suppressed in response to shade conditions. This suppression of tiller and lateral branch growth is an important trait selected by early agriculturalists during maize domestication and crop improvement. To understand how plants integrate external environmental cues with endogenous signals to control their architecture, we have begun a functional characterization of the maize mutant
grassy tillers1
(
gt1
). We isolated the
gt1
gene using positional cloning and found that it encodes a class I homeodomain leucine zipper gene that promotes lateral bud dormancy and suppresses elongation of lateral ear branches. The
gt1
expression is induced by shading and is dependent on the activity of
teosinte branched1
(
tb1
), a major domestication locus controlling tillering and lateral branching. Interestingly, like
tb1
,
gt1
maps to a quantitative trait locus that regulates tillering and lateral branching in maize and shows evidence of selection during maize domestication. Branching and shade avoidance are both of critical agronomic importance, but little is known about how these processes are integrated. Our results indicate that
gt1
mediates the reduced branching associated with the shade avoidance response in the grasses. Furthermore, selection at the
gt1
locus suggests that it was involved in improving plant architecture during the domestication of maize.
Social conflict drives the evolutionary divergence of quorum sensing
Authors: Eldar Avigdor
Published: August 2011

In microbial “quorum sensing” (QS) communication systems, microbes produce and respond to a signaling molecule, enabling a cooperative response at high cell densities. Many species of bacteria show fast, intraspecific, evolutionary divergence of their QS pathway specificity—signaling molecules activate cognate receptors in the same strain but fail to activate, and sometimes inhibit, those of other strains. Despite many molecular studies, it has remained unclear how a signaling molecule and receptor can coevolve, what maintains diversity, and what drives the evolution of cross-inhibition. Here I use mathematical analysis to show that when QS controls the production of extracellular enzymes —“public goods”—diversification can readily evolve. Coevolution is positively selected by cycles of alternating “cheating” receptor mutations and “cheating immunity” signaling mutations. The maintenance of diversity and the evolution of cross-inhibition between strains are facilitated by facultative cheating between the competing strains. My results suggest a role for complex social strategies in the long-term evolution of QS systems. More generally, my model of QS divergence suggests a form of kin recognition where different kin types coexist in unstructured populations.
Light enhances learned fear
Authors: Warthen Daniel M. , Wiltgen Brian J. , Provencio Ignacio
Published: August 2011

The ability to learn, remember, and respond to emotional events is a powerful survival strategy. However, dysregulated behavioral and physiological responses to these memories are maladaptive. To fully understand learned fear and the pathologies that arise during response malfunction we must reveal the environmental variables that influence learned fear responses. Light, a ubiquitous environmental feature, modulates cognition and anxiety. We hypothesized that light modulates responses to learned fear. Using tone-cued fear conditioning, we found that light enhances behavioral responses to learned fear in C57BL/6J mice. Mice in light freeze more in response to a conditioned cue than mice in darkness. The absence of significant freezing during a 2-wk habituation period and during intertrial intervals indicated that light specifically modulates freezing to the learned acoustic cue rather than the context of the experimental chamber. Repeating our assay in two photoreceptor mutant models,

Pde6b
rd1/rd1

and

Opn4
−/−

mice, revealed that light-dependent enhancement of conditioned fear is driven primarily by the rods and/or cones. By repeating our protocol with an altered lighting regimen, we found that lighting conditions acutely modulate responses when altered between conditioning and testing. This is manifested either as an enhancement of freezing when light is added during testing or as a depression of freezing when light is removed during testing. Acute enhancement, but not depression, requires both rod/cone- and melanopsin-dependent photoreception. Our results demonstrate a modulation by light of behavioral responses to learned fear.
In vivo molecular imaging of peripheral amyloidosis using heparin-binding peptides
Authors: Wall Jonathan S. , Richey Tina , Stuckey Alan , Donnell Robert , Macy Sallie , Martin Emily B. , Williams Angela , Higuchi Keiichi , Kennel Stephen J.
Published: August 2011

Heparan sulfate proteoglycans (HSPGs) are ubiquitous components of pathologic amyloid deposits in the organs of patients with disorders such as Alzheimer's disease or systemic light chain (AL) or reactive (AA) amyloidosis. Molecular imaging methods for early detection are limited and generally unavailable outside the United Kingdom. Therefore, there is an urgent need to develop novel, specific amyloidophilic radiotracers for imaging to assist in diagnosis, prognostication, and monitoring response to therapy. Amyloid-associated HSPG can be differentiated from HSPG found in surrounding healthy cells and tissues by the preferential binding of certain HS-reactive single chain variable fragments and therefore, represents a biomarker that can be targeted specifically with appropriate reagents. Using a murine model of AA amyloidosis, we have examined the in vivo amyloid reactivity of seven heparin-binding peptides by using single photon emission and X-ray computed tomographic imaging, microautoradiography, and tissue biodistribution measurements. All of the peptides bound amyloid deposits within 1 h post-injection, but the extent of the reactivity differed widely, which was evidenced by image quality and grain density in autoradiographs. One radiolabeled peptide bound specifically to murine AA amyloid in the liver, spleen, kidney, adrenal, heart, and pancreas with such avidity that it was observed in single photon emission tomography images as late as 24 h post-injection. In addition, a biotinylated form of this peptide was shown histochemically to bind human AA, ALκ, ALλ, transthyretin amyloidosis (ATTR), and Aβ amyloid deposits in tissue sections. These basic heparin-binding peptides recognize murine and human amyloid deposits in both in vivo and ex vivo tissues and therefore, have potential as radiotracers for the noninvasive molecular imaging of amyloid deposits in situ.
The Ca
V
3.3 calcium channel is the major sleep spindle pacemaker in thalamus
Authors: Astori Simone , Wimmer Ralf D. , Prosser Haydn M. , Corti Corrado , Corsi Mauro , Liaudet Nicolas , Volterra Andrea , Franken Paul , Adelman John P. , Lüthi Anita
Published: August 2011

Low-threshold (T-type) Ca
2+
channels encoded by the

Ca
V
3

genes endow neurons with oscillatory properties that underlie slow waves characteristic of the non-rapid eye movement (NREM) sleep EEG. Three Ca
V
3 channel subtypes are expressed in the thalamocortical (TC) system, but their respective roles for the sleep EEG are unclear. Ca
V
3.3 protein is expressed abundantly in the nucleus reticularis thalami (nRt), an essential oscillatory burst generator. We report the characterization of a transgenic

Ca
V
3.3

−
/
−

mouse line and demonstrate that Ca
V
3.3 channels are indispensable for nRt function and for sleep spindles, a hallmark of natural sleep. The absence of Ca
V
3.3 channels prevented oscillatory bursting in the low-frequency (4–10 Hz) range in nRt cells but spared tonic discharge. In contrast, adjacent TC neurons expressing Ca
V
3.1 channels retained low-threshold bursts. Nevertheless, the generation of synchronized thalamic network oscillations underlying sleep-spindle waves was weakened markedly because of the reduced inhibition of TC neurons via nRt cells. T currents in

Ca
V
3.3

−
/
−

mice were <30% compared with those in WT mice, and the remaining current, carried by Ca
V
3.2 channels, generated dendritic [Ca
2+
]
i
signals insufficient to provoke oscillatory bursting that arises from interplay with Ca
2+
-dependent small conductance-type 2 K
+
channels. Finally, naturally sleeping

Ca
V
3.3

−
/
−

mice showed a selective reduction in the power density of the σ frequency band (10–12 Hz) at transitions from NREM to REM sleep, with other EEG waves remaining unaltered. Together, these data identify a central role for Ca
V
3.3 channels in the rhythmogenic properties of the sleep-spindle generator and provide a molecular target to elucidate the roles of sleep spindles for brain function and development.
Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function
Authors: Suzuki Kunihiro , Olah Gabor , Modis Katalin , Coletta Ciro , Kulp Gabriella , Gerö Domokos , Szoleczky Petra , Chang Tuanjie , Zhou Zongmin , Wu Lingyun , Wang Rui , Papapetropoulos Andreas , Szabo Csaba
Published: August 2011

The goal of the present studies was to investigate the role of changes in hydrogen sulfide (H2S) homeostasis in the pathogenesis of hyperglycemic endothelial dysfunction. Exposure of bEnd3 microvascular endothelial cells to elevated extracellular glucose (in vitro “hyperglycemia”) induced the mitochondrial formation of reactive oxygen species (ROS), which resulted in an increased consumption of endogenous and exogenous H2S. Replacement of H2S or overexpression of the H2S-producing enzyme cystathionine-γ-lyase (CSE) attenuated the hyperglycemia-induced enhancement of ROS formation, attenuated nuclear DNA injury, reduced the activation of the nuclear enzyme poly(ADP-ribose) polymerase, and improved cellular viability. In vitro hyperglycemia resulted in a switch from oxidative phosphorylation to glycolysis, an effect that was partially corrected by H2S supplementation. Exposure of isolated vascular rings to high glucose in vitro induced an impairment of endothelium-dependent relaxations, which was prevented by CSE overexpression or H2S supplementation. siRNA silencing of CSE exacerbated ROS production in hyperglycemic endothelial cells. Vascular rings from CSE−/−mice exhibited an accelerated impairment of endothelium-dependent relaxations in response to in vitro hyperglycemia, compared with wild-type controls. Streptozotocin-induced diabetes in rats resulted in a decrease in the circulating level of H2S; replacement of H2S protected from the development of endothelial dysfunction ex vivo. In conclusion, endogenously produced H2S protects against the development of hyperglycemia-induced endothelial dysfunction. We hypothesize that, in hyperglycemic endothelial cells, mitochondrial ROS production and increased H2S catabolism form a positive feed-forward cycle. H2S replacement protects against these alterations, resulting in reduced ROS formation, improved endothelial metabolic state, and maintenance of normal endothelial function.
High-speed microscopic imaging of flagella motility and swimming in
Giardia lamblia
trophozoites
Authors: Lenaghan Scott C. , Davis Corinne A. , Henson William R. , Zhang Zhili , Zhang Mingjun
Published: August 2011

We report, in this paper, several findings about the swimming and attachment mechanisms of
Giardia lamblia
trophozoites. These data were collected using a combination of a high-contrast CytoViva imaging system and a particle image velocimetry camera, which can capture images at speeds greater than 800 frames/s. Using this system, we discovered that, during rapid swimming of
Giardia
trophozoites, undulations of the caudal region contributed to forward propulsion combined with the beating of the flagella pairs. It was also discovered, in contrast to previous studies with 10 times slower image sampling technique, that the anterior and posterolateral flagella beat with a clearly defined power stroke and not symmetrical undulations. During the transition from free swimming to attachment, trophozoites modified their swimming behavior from a rapid rotating motion to a more stable planar swimming. While using this planar swimming motion, the trophozoites used the flagella for propulsion and directional control. In addition to examination of the posterolateral and anterior flagella, a model to describe the motion of the ventral flagella was derived, indicating that the ventral flagella beat in an expanding sine wave. In addition, the structure of the ventrocaudal groove creates boundary conditions that determine the form of beating of the ventral flagella. The results from this study indicate that
Giardia
is able to simultaneously generate both ciliary beating and typical eukaryotic flagellar beating using different pairs of flagella.
Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue
Authors: Stringari Chiara , Cinquin Amanda , Cinquin Olivier , Digman Michelle A. , Donovan Peter J. , Gratton Enrico
Published: August 2011

We describe a label-free imaging method to monitor stem-cell metabolism that discriminates different states of stem cells as they differentiate in living tissues. In this method we use intrinsic fluorescence biomarkers and the phasor approach to fluorescence lifetime imaging microscopy in conjunction with image segmentation, which we use to introduce the concept of the cell phasor. In live tissues we are able to identify intrinsic fluorophores, such as collagen, retinol, retinoic acid, porphyrin, flavins, and free and bound NADH. We have exploited the cell phasor approach to detect a trend in metabolite concentrations along the main axis of the
Caenorhabditis elegans
germ line. This trend is consistent with known changes in metabolic states during differentiation. The cell phasor approach to lifetime imaging provides a label-free, fit-free, and sensitive method to identify different metabolic states of cells during differentiation, to sense small changes in the redox state of cells, and may identify symmetric and asymmetric divisions and predict cell fate. Our method is a promising noninvasive optical tool for monitoring metabolic pathways during differentiation or disease progression, and for cell sorting in unlabeled tissues.
Genetic framework for GATA factor function in vascular biology
Authors: Linnemann Amelia K. , O’Geen Henriette , Keles Sunduz , Farnham Peggy J. , Bresnick Emery H.
Published: August 2011

Vascular endothelial dysfunction underlies the genesis and progression of numerous diseases. Although the GATA transcription factor GATA-2 is expressed in endothelial cells and is implicated in coronary heart disease, it has been studied predominantly as a master regulator of hematopoiesis. Because many questions regarding GATA-2 function in the vascular biology realm remain unanswered, we used ChIP sequencing and loss-of-function strategies to define the GATA-2–instigated genetic network in human endothelial cells. In contrast to erythroid cells, GATA-2 occupied a unique target gene ensemble consisting of genes encoding key determinants of endothelial cell identity and inflammation. GATA-2–occupied sites characteristically contained motifs that bind activator protein-1 (AP-1), a pivotal regulator of inflammatory genes. GATA-2 frequently occupied the same chromatin sites as c-JUN and c-FOS, heterodimeric components of AP-1. Although all three components were required for maximal AP-1 target gene expression, GATA-2 was not required for AP-1 chromatin occupancy. GATA-2 conferred maximal phosphorylation of chromatin-bound c-JUN at Ser-73, which stimulates AP-1–dependent transactivation, in a chromosomal context-dependent manner. This work establishes a link between a GATA factor and inflammatory genes, mechanistic insights underlying GATA-2–AP-1 cooperativity and a rigorous genetic framework for understanding GATA-2 function in normal and pathophysiological vascular states.
Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation
Authors: Sertic Sarah , Pizzi Sara , Cloney Ross , Lehmann Alan R. , Marini Federica , Plevani Paolo , Muzi-Falconi Marco
Published: August 2011

UV light induces DNA lesions, which are removed by nucleotide excision repair (NER). Exonuclease 1 (EXO1) is highly conserved from yeast to human and is implicated in numerous DNA metabolic pathways, including repair, recombination, replication, and telomere maintenance. Here we show that hEXO1 is involved in the cellular response to UV irradiation in human cells. After local UV irradiation, fluorescent-tagged hEXO1 localizes, together with NER factors, at the sites of damage in nonreplicating cells. hEXO1 accumulation requires XPF-dependent processing of UV-induced lesions and is enhanced by inhibition of DNA repair synthesis. In nonreplicating cells, depletion of hEXO1 reduces unscheduled DNA synthesis after UV irradiation, prevents ubiquitylation of histone H2A, and impairs activation of the checkpoint signal transduction cascade in response to UV damage. These findings reveal a key role for hEXO1 in the UV-induced DNA damage response linking NER to checkpoint activation in human cells.
Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA
Authors: Kukat Christian , Wurm Christian A. , Spåhr Henrik , Falkenberg Maria , Larsson Nils-Göran , Jakobs Stefan
Published: August 2011

Mammalian mtDNA is packaged in DNA-protein complexes denoted mitochondrial nucleoids. The organization of the nucleoid is a very fundamental question in mitochondrial biology and will determine tissue segregation and transmission of mtDNA. We have used a combination of stimulated emission depletion microscopy, enabling a resolution well below the diffraction barrier, and molecular biology to study nucleoids in a panel of mammalian tissue culture cells. We report that the nucleoids labeled with antibodies against DNA, mitochondrial transcription factor A (TFAM), or incorporated BrdU, have a defined, uniform mean size of ∼100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average ∼1.4 mtDNA molecules per nucleoid). Furthermore, we show by molecular modeling and volume calculations that TFAM is a main constituent of the nucleoid, besides mtDNA. These fundamental insights into the organization of mtDNA have broad implications for understanding mitochondrial dysfunction in disease and aging.
Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals
Authors: Rabøl Rasmus , Petersen Kitt Falk , Dufour Sylvie , Flannery Clare , Shulman Gerald I.
Published: August 2011

Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postprandial energy storage. We conducted a study to examine this hypothesis by reversing muscle insulin resistance with a single bout of exercise and measuring hepatic de novo lipogenesis and hepatic triglyceride synthesis after a carbohydrate-rich meal. We studied 12 healthy, young, lean, insulin resistant individuals in an interventional, randomized cross-over trial. The response to the ingestion of a carbohydrate-rich meal was studied at rest and after one 45-min bout of exercise on an elliptical trainer. Hepatic de novo lipogenesis was assessed by using
2
H
2
O, and changes in glycogen and fat content in liver and muscle were measured by
13
C and
1
H magnetic resonance spectroscopy, respectively. Exercise resulted in a greater than threefold increase in postprandial net muscle glycogen synthesis (
P
< 0.001), reflecting improved muscle insulin responsiveness, and a ≈40% reduction (
P
< 0.05) in net hepatic triglyceride synthesis. These changes in whole body energy storage were accompanied by a ≈30% decrease in hepatic de novo lipogenesis (
P
< 0.01) and were independent of changes in fasting or postprandial plasma glucose and insulin concentrations. These data demonstrate that skeletal muscle insulin resistance is an early therapeutic target for the treatment and prevention of atherogenic dyslipidemia and NAFLD in young insulin resistant individuals who are prone to develop the metabolic syndrome and type 2 diabetes.
Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function
Authors: Etherton Mark , Földy Csaba , Sharma Manu , Tabuchi Katsuhiko , Liu Xinran , Shamloo Mehrdad , Malenka Robert C. , Südhof Thomas C.
Published: August 2011

Multiple independent mutations in neuroligin genes were identified in patients with familial autism, including the R451C substitution in neuroligin-3 (NL3). Previous studies showed that NL3
R451C
knock-in mice exhibited modestly impaired social behaviors, enhanced water maze learning abilities, and increased synaptic inhibition in the somatosensory cortex, and they suggested that the behavioral changes in these mice may be caused by a general shift of synaptic transmission to inhibition. Here, we confirm that NL3
R451C
mutant mice behaviorally exhibit social interaction deficits and electrophysiologically display increased synaptic inhibition in the somatosensory cortex. Unexpectedly, however, we find that the NL3
R451C
mutation produced a strikingly different phenotype in the hippocampus. Specifically, in the hippocampal CA1 region, the NL3
R451C
mutation caused an ∼1.5-fold increase in AMPA receptor-mediated excitatory synaptic transmission, dramatically altered the kinetics of NMDA receptor-mediated synaptic responses, induced an approximately twofold up-regulation of NMDA receptors containing NR2B subunits, and enhanced long-term potentiation almost twofold. NL3 KO mice did not exhibit any of these changes. Quantitative light microscopy and EM revealed that the NL3
R451C
mutation increased dendritic branching and altered the structure of synapses in the stratum radiatum of the hippocampus. Thus, in NL3
R451C
mutant mice, a single point mutation in a synaptic cell adhesion molecule causes context-dependent changes in synaptic transmission; these changes are consistent with the broad impact of this mutation on murine and human behaviors, suggesting that NL3 controls excitatory and inhibitory synapse properties in a region- and circuit-specific manner.
PARP regulates nonhomologous end joining through retention of Ku at double-strand breaks
Authors: Couto C. Anne-Marie , Wang Hong-Yu , Green Joanna C.A. , Kiely Rhian , Siddaway Robert , Borer Christine , Pears Catherine J. , Lakin Nicholas D.
Published: August 2011

Poly adenosine diphosphate (ADP)–ribosylation (PARylation) by poly ADP-ribose (PAR) polymerases (PARPs) is an early response to DNA double-strand breaks (DSBs). In this paper, we exploit Dictyostelium discoideum to uncover a novel role for PARylation in regulating nonhomologous end joining (NHEJ). PARylation occurred at single-strand breaks, and two PARPs, Adprt1b and Adprt2, were required for resistance to this kind of DNA damage. In contrast, although Adprt1b was dispensable for PARylation at DSBs, Adprt1a and, to a lesser extent, Adprt2 were required for this event. Disruption of adprt2 had a subtle impact on the ability of cells to perform NHEJ. However, disruption of adprt1a decreased the ability of cells to perform end joining with a concomitant increase in homologous recombination. PAR-dependent regulation of NHEJ was achieved through promoting recruitment and/or retention of Ku at DSBs. Furthermore, a PAR interaction motif in Ku70 was required for this regulation and efficient NHEJ. These data illustrate that PARylation at DSBs promotes NHEJ through recruitment or retention of repair factors at sites of DNA damage.