bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4
Authors: Tietjen Gregory T. , Gong Zhiliang , Chen Chiu-Hao , Vargas Ernesto , Crooks James E. , Cao Kathleen D. , Heffern Charles T. R. , Henderson J. Michael , Meron Mati , Lin Binhua , Roux Benoît , Schlossman Mark L. , Steck Theodore L. , Lee Ka Yee C. , Adams Erin J. 
Published: April 2014

Significance
Structural immunology employs static, atomic-level representations to uncover the molecular mechanisms by which immune receptors sensitively discern infection and disease. Lipid membranes, particularly those exposing phosphatidylserine lipids, are now understood to be important signals in various aspects of immune regulation. However, the dynamic nature of lipid membranes makes the standard tools of structural immunology poorly suited to these systems, leaving a large gap in our understanding. Here we implement a suite of multidisciplinary tools to demonstrate, for the first time to the authors' knowledge, a mechanism for sensitivity of an immune regulatory receptor (Tim4) to the membrane context of phosphatidylserine exposure. These findings uncover new aspects of Tim4’s recognition properties and, perhaps more significantly, provide a methodology for obtaining atomic-level detail in membrane recognition.
Heat shock protein 90 controls HIV-1 reactivation from latency
Authors: Anderson Ian , Low Jun Siong , Weston Stuart , Weinberger Michael , Zhyvoloup Alexander , Labokha Aksana A. , Corazza Gianmarco , Kitson Russell A. , Moody Christopher J. , Marcello Alessandro , Fassati Ariberto 
Published: April 2014

SignificanceAntiretroviral therapy cannot eradicate HIV-1 because the virus can become transcriptionally inactive in resting memory CD4+ T cells (and other cell types), which are long-lived, thus generating a reservoir undetectable by the immune system. When therapy is stopped, the latent viral reservoir is activated and HIV-1 rebounds. Our understanding of HIV-1 latency and reactivation is incomplete. Here we report that the heat shock protein 90 (Hsp90) regulates HIV-1 reactivation from latency by controlling the NF-kB pathway. Therefore Hsp90 is a key molecule linking HIV-1 reactivation from latency to CD4+ T-cell activation. Selective Hsp90 inhibitors combined with PKC-ϑ inhibitors, all in phase II clinical trials, potently suppressed HIV-1 reactivation, thus Hsp90 may be a novel target to control HIV-1 latency.
Language learners privilege structured meaning over surface frequency
Authors: Culbertson Jennifer , Adger David 
Published: April 2014

SignificanceHow humans represent aspects of the grammar of the languages they speak is a fundamental question in psychology and linguistics. Two kinds of proposals have been made: One posits abstract structural representations, while the other takes the relevant generalizations to be stated over surface statistical regularities from data learners are exposed to. Our results, based on artificial language learning experiments, show that language learners, when confronted with a new linguistic system, systematically privilege structural similarity to their native language over surface statistical similarity. We propose that the relevant structural bias is one that prefers word order and meaning to line up in a particular way.
Microtubule binding distinguishes dystrophin from utrophin
Authors: Belanto Joseph J. , Mader Tara L. , Eckhoff Michael D. , Strandjord Dana M. , Banks Glen B. , Gardner Melissa K. , Lowe Dawn A. , Ervasti James M. 
Published: April 2014

Significance
Our in vitro analyses reveal that dystrophin, the protein absent in Duchenne muscular dystrophy patients, binds microtubules with high affinity and pauses microtubule polymerization, whereas utrophin, the autosomal homologue of dystrophin thought to mirror many known functions of dystrophin, has no activity in either assay. We also report that transgenic utrophin overexpression does not correct subsarcolemmal microtubule lattice disorganization, physical inactivity after mild exercise, or loss of torque production after in vivo eccentric contraction in dystrophin-deficient skeletal muscle. Finally, our data demonstrate that microtubule lattice disorganization contributes to the greater eccentric contraction-induced injury experienced by dystrophin-deficient skeletal muscle, demonstrating a phenotype of dystrophin deficiency that utrophin-based therapy may not be able to correct.
Differential ubiquitination and degradation of huntingtin fragments modulated by ubiquitin-protein ligase E3A
Authors: Bhat Kavita P. , Yan Sen , Wang Chuan-En , Li Shihua , Li Xiao-Jiang 
Published: April 2014

Significance
Ubiquitination of misfolded proteins is an important process in a variety of age-dependent neurodegenerative diseases including Alzheimer’s disease, Parkinson disease, and Huntington disease (HD). However, we know little about how ubiquitination regulates the degradation and accumulation of misfolded proteins. By using HD knock-in mice and cultured cells, we found that the pathogenic form of the HD protein is differentially ubiquitinated via K48 and K63 in ubiquitin. K48-mediated ubiquitination promotes huntingtin (Htt) degradation while K63-mediated ubiquitination accelerates its aggregation. The K-48–mediated ubiquitination depends on Ube3a, whose expression declines in aged brain. Overexpression of Ube3a in old HD KI mouse brain can reduce mutant Htt accumulation and aggregation. The age-dependent decline in Ube3a may contribute to the late-onset neuropathology in HD.
Higher-order dangers and precisely constructed taxa in models of randomness
Authors: Pincus Steve , Singer Burton H. 
Published: April 2014

Significance
The validation and construction of individual, putatively “random” infinite sequences have been longstanding problems within mathematics. We address this topic via the study of binary normal numbers, which often have been viewed as models for randomness. We show that normality exhibits a rich, multifactorial taxonomy and is hardly a single monochromatic category. Furthermore, we present a toolkit of algorithmic techniques to explicitly construct normal sequences to achieve diverse yet precisely controlled specifications, many of which (e.g., bias) display unexpected and somewhat pathologic subordinate dynamics. Moreover, we construct a normal number that exhibits pairwise bias toward repeated values and, accordingly, deduce that the evaluation of higher-order block behavior, even beyond equidistribution, is imperative in proper evaluations of “randomness.”
Susceptibility to Myxobolus cerebralis among Tubifex tubifex Populations from Ten Major Drainage Basins in Colorado Where Cutthroat Trout Are Endemic
Authors: Nehring R. Barry , Lukacs P. M. , Baxa D. V. , Stinson M. E. T. , Chiaramonte L. , Wise S. K. , Poole B. , Horton A. 
Published: April 2014

Abstract
Establishment of Myxobolus cerebralis (Mc) resulted in declines of wild Rainbow Trout Oncorhynchus mykiss populations in streams across Colorado during the 1990s. However, the risk for establishment and spread of this parasite into high-elevation habitats occupied by native Cutthroat Trout O. clarkii was unknown. Beginning in 2003, tubificid worms were collected from all major drainages where Cutthroat Trout were endemic and were assayed by quantitative PCR to determine the occurrence and distribution of the various lineages of Tubifex tubifex (Tt) oligochaetes. Over a 5-year period, 40 groups of Tt oligochaetes collected from 27 streams, 3 natural lakes, 2 private ponds, and a reservoir were evaluated for their relative susceptibility to Mc. Exposure groups were drawn from populations of pure lineage III Tt, mixed-lineage populations where one or more of the highly resistant (lineage I) or nonsusceptible lineages (V or VI) were the dominant oligochaete and susceptible lineage III worms were the subdominant worm, or pure lineage VI Tt. Experimental replicates of 250 oligochaetes were exposed to 50 Mc myxospores per worm. The parasite amplification ratio (total triactinomyxons [TAMs] produced / total myxospore exposure) was very high among all pure lineage III Colorado exposure groups, averaging 363 compared with 8.24 among the mixed-lineage exposure groups. Lineage III oligochaetes from Mt. Whitney Hatchery in California, which served as the laboratory standard for comparative purposes, had an average parasite amplification ratio of 933 among 10 exposed replicates over a 5-year period. Lineage I oligochaetes were highly resistant to infection and did not produce any TAMs. Lineages V and VI Tt did not become infected and did not produce any TAMs. These results suggest that the risk of establishment of Mc is high for aquatic habitats in Colorado where Cutthroat Trout and lineage III Tt are sympatric.
Received April 19, 2013; accepted November 4, 2013
Small zeros of quadratic forms outside a union of varieties
Authors: Chan Wai Kiu , Fukshansky Lenny , Henshaw Glenn 
Published: April 2014

Let

F
F

be a quadratic form in

N
≥
2

N \geq 2

variables defined on a vector space

V
⊆

K
N

V \subseteq K^N

over a global field

K
K

, and

Z

⊆

K
N

\mathcal {Z} \subseteq K^N

be a finite union of varieties defined by families of homogeneous polynomials over

K
K

. We show that if

V
∖

Z

V \setminus \mathcal {Z}

contains a nontrivial zero of

F
F

, then there exists a linearly independent collection of small-height zeros of

F
F

in

V
∖

Z

V\setminus \mathcal {Z}

, where the height bound does not depend on the height of

Z

\mathcal {Z}

, only on the degrees of its defining polynomials. As a corollary of this result, we show that there exists a small-height maximal totally isotropic subspace

W
W

of the quadratic space

(
V
,
F
)

(V,F)

such that

W
W

is not contained in

Z

\mathcal {Z}

. Our investigation extends previous results on small zeros of quadratic forms, including Cassels’ theorem and its various generalizations. The paper also contains an appendix with two variations of Siegel’s lemma. All bounds on height are explicit.
The dynamics of fish populations at low abundance and prospects for rebuilding and recovery
Authors: Hilborn Ray , Hively Daniel J. , Jensen Olaf P. , Branch Trevor A. 
Published: April 2014

Abstract
Previous meta-analysis of spawner–recruit relationships suggested that depensatory behaviour is uncommon, and stocks pushed to low abundance are unlikely to suffer decreases in recruitment more severe than would be expected based on the decline in spawning stock. Using an updated database that has over 100 stocks that were depleted to less than 20% of their maximum observed stock size, we tested for depensatory behaviour in both total surplus production and recruitment and we also examined the probability of stock increase as a function of stock size and fishing pressure. The number of stocks that showed a significant improvement with depensatory models was less than that expected by chance. Hierarchical meta-analysis showed that the majority of the evidence was for no depensatory behaviour but could not rule out depensation at very low stock sizes. Stocks that are depleted to low abundance are expected to rebuild when fishing pressure is reduced if the environment has not changed but there is considerable evidence that the majority of fish stocks are impacted by changes in productivity regimes. Nevertheless, if stocks are very heavily depleted and fishing pressure is not reduced to quite low levels, the expected recovery time is both uncertain and long. Very low abundance should clearly be avoided for many reasons and the range of abundance where depensation cannot be ruled out is well below commonly adopted limit reference points.
Secreted Fungal Effector Lipase Releases Free Fatty Acids to Inhibit Innate Immunity-Related Callose Formation during Wheat Head Infection
Authors: Blümke Antje , Falter Christian , Herrfurth Cornelia , Sode Björn , Bode Rainer , Schäfer Wilhelm , Feussner Ivo , Voigt Christian A. 
Published: April 2014

Abstract
The deposition of the (1,3)-β-glucan cell wall polymer callose at sites of attempted penetration is a common plant defense response to intruding pathogens and part of the plant’s innate immunity. Infection of the Fusarium graminearum disruption mutant Ɗfgl1, which lacks the effector lipase FGL1, is restricted to inoculated wheat (Triticum aestivum) spikelets, whereas the wild-type strain colonized the whole wheat spike. Our studies here were aimed at analyzing the role of FGL1 in establishing full F. graminearum virulence. Confocal laser-scanning microscopy revealed that the Ɗfgl1 mutant strongly induced the deposition of spot-like callose patches in vascular bundles of directly inoculated spikelets, while these callose deposits were not observed in infections by the wild type. Elevated concentrations of the polyunsaturated free fatty acids (FFAs) linoleic and α-linolenic acid, which we detected in F. graminearum wild type-infected wheat spike tissue compared with Ɗfgl1-infected tissue, provided clear evidence for a suggested function of FGL1 in suppressing callose biosynthesis. These FFAs not only inhibited plant callose biosynthesis in vitro and in planta but also partially restored virulence to the Ɗfgl1 mutant when applied during infection of wheat spikelets. Additional FFA analysis confirmed that the purified effector lipase FGL1 was sufficient to release linoleic and α-linolenic acids from wheat spike tissue. We concluded that these two FFAs have a major function in the suppression of the innate immunity-related callose biosynthesis and, hence, the progress of F. graminearum wheat infection.
Fitting occupancy models with E‐SURGE: hidden Markov modelling of presence–absence data
Authors: Gimenez Olivier , Blanc Laetitia , Besnard Aurélien , Pradel Roger , Doherty Paul F. , Marboutin Eric , Choquet Rémi 
Published: April 2014

Summary

Occupancy – the proportion of area occupied by a species – is a key notion for addressing important questions in ecology, biogeography and conservation biology. Occupancy models allow estimating and inferring about species occurrence while accounting for false absences (or imperfect species detection).

Occupancy models can be formulated as hidden Markov models (HMM) in which the state process captures the Markovian dynamic of the actual but latent states, while the observation process consists of observations that are made from these underlying states.

We show how occupancy models can be implemented in program E‐SURGE, which was initially developed to analyse capture–recapture data in the HMM framework. Replacing individuals by sites provides the user with access to several features of E‐SURGE that are not available altogether or just not available in standard occupancy software: i) flexible model specification through a user‐friendly syntax without having to write custom code, ii) decomposition of the observation and state processes in several steps to provide flexible parameterisation, iii) up‐to‐date diagnostics of model identifiability, and iv) advanced numerical algorithms to produce fast and reliable results (including site random effects).

To illustrate E‐SURGE features, we provide implementation and analysis details for several occupancy models. We also provide simulated and real‐world examples as well as further specifications and information in a companion wiki platform http://occupancyinesurge.wikidot.com/.
Third Trimester‐Equivalent Ethanol Exposure Does Not Alter Complex Spikes and Climbing Fiber Long‐Term Depression in Cerebellar Purkinje Neurons from Juvenile Rats
Authors: Zamudio‐Bulcock Paula A. , Morton Russell A. , Valenzuela C. Fernando 
Published: April 2014

BackgroundStudies indicate that exposure to ethanol (EtOH) during fetal development damages cerebellar Purkinje cells (PCs). PC proximal dendrites receive glutamatergic input from climbing fibers (CFs) originating at the inferior olive. CF input produces a characteristic response in PCs known as the complex spike (CS). During the first 2 weeks of life in rodents (equivalent to the human third trimester of pregnancy), CF–PC synapses undergo profound refinement. Here, we characterized the impact of EtOH exposure during this period on CF‐evoked responses in PCs.MethodsUsing vapor chambers, neonatal rat pups and their mothers were exposed to air or EtOH for 4 h/d between postnatal day 2 (P2) and P12 (pup serum EtOH concentration, 0.16 g/dl). The function of CF–PC synapses was characterized using patch‐clamp electrophysiological techniques in acute slices from the cerebellar vermis. Experiments were performed soon after EtOH withdrawal, when perisomatic CFs are still being eliminated (P15 to P17), and after weaning when CF dendritic translocation is almost complete (P21 to P34).ResultsNeither the baseline characteristics of the CS (Na+ spike amplitude, area, coastline index, and afterhyperpolarization [AHP] amplitude) nor the type‐1 metabotropic glutamate receptor (mGluR1)‐mediated component of both the CS and AHP were significantly affected by EtOH exposure at P15 to P17 or P21 to P34. The mGluR1‐dependent long‐term depression (LTD) of CF‐evoked excitatory postsynaptic currents was not significantly affected by EtOH exposure at P21 to P34.ConclusionsEtOH exposure during the third trimester equivalent neither affected basal characteristics of the CS nor CF‐LTD at rat cerebellar PCs from juvenile rats.
Using Facebook to deliver a social norm intervention to reduce problem drinking at university
Authors: Ridout Brad , Campbell Andrew 
Published: April 2014

AbstractIntroduction and AimsUniversity students usually overestimate peer alcohol use, resulting in them ‘drinking up’ to perceived norms. Social norms theory suggests correcting these inflated perceptions can reduce alcohol consumption. Recent findings by the current authors show portraying oneself as ‘a drinker’ is considered by many students to be a socially desirable component of their Facebook identity, perpetuating an online culture that normalises binge drinking. However, social networking sites have yet to be utilised in social norms interventions.Design and MethodsActual and perceived descriptive and injunctive drinking norms were collected from 244 university students. Ninety‐five students screened positive for hazardous drinking and were randomly allocated to a control group or intervention group that received social norms feedback via personalised Facebook private messages over three sessions.ResultsAt 1 month post‐intervention, the quantity and frequency of alcohol consumed by intervention group during the previous month had significantly reduced compared with baseline and controls. Reductions were maintained 3 months post‐intervention. Intervention group perceived drinking norms were significantly more accurate post‐intervention.Discussion and ConclusionsThis is the first study to test the feasibility of using Facebook to deliver social norms interventions. Correcting misperceptions of peer drinking norms resulted in clinically significant reductions in alcohol use. Facebook has many advantages over traditional social norms delivery, providing an innovative method for tackling problem drinking at university. These results have implications for the use of Facebook to deliver positive messages about safe alcohol use to students, which may counter the negative messages regarding alcohol normally seen on Facebook. [Ridout B, Campbell A. Using Facebook to deliver a social norm intervention to reduce problem drinking at university. Drug Alcohol Rev 2014;33:667–73]
A switch from inter‐ocular to inter‐hemispheric suppression following monocular deprivation in the rat visual cortex
Authors: Pietrasanta Marta , Restani Laura , Cerri Chiara , Olcese Umberto , Medini Paolo , Caleo Matteo 
Published: April 2014

AbstractBinocularity is a key property of primary visual cortex (V1) neurons that is widely used to study synaptic integration in the brain and plastic mechanisms following an altered visual experience. However, it is not clear how the inputs from the two eyes converge onto binocular neurons, and how their interaction is modified by an unbalanced visual drive. Here, using visual evoked potentials recorded in the juvenile rat V1, we report evidence for a suppressive mechanism by which contralateral eye activity inhibits responses from the ipsilateral eye. Accordingly, we found a lack of additivity of the responses evoked independently by the two eyes in the V1, and acute silencing of the contralateral eye resulted in the enhancement of ipsilateral eye responses in cortical neurons. We reverted the relative cortical strength of the two eyes by suturing the contralateral eye shut [monocular deprivation (MD)]. After 7 days of MD, there was a loss of interocular suppression mediated by the contralateral, deprived eye, and weak inputs from the closed eye were functionally inhibited by interhemispheric callosal pathways. We conclude that interocular suppressive mechanisms play a crucial role in shaping normal binocularity in visual cortical neurons, and a switch from interocular to interhemispheric suppression represents a key step in the ocular dominance changes induced by MD. These data have important implications for a deeper understanding of the key mechanisms that underlie activity‐dependent rearrangements of cortical circuits following alteration of sensory experience.
Life‐history syndromes: Integrating dispersal through space and time
Authors: Buoro Mathieu , Carlson Stephanie M. 
Published: April 2014

AbstractRecent research has highlighted interdependencies between dispersal and other life‐history traits, i.e. dispersal syndromes, thereby revealing constraints on the evolution of dispersal and opportunities for improved ability to predict dispersal by considering suites of dispersal‐related traits. This review adds to the growing list of life‐history traits linked to spatial dispersal by emphasising the interdependence between dispersal through space and time, i.e. life‐history diversity that distributes individuals into separate reproductive events. We reviewed the literature that has simultaneously investigated spatial and temporal dispersal to examine the prediction that traits of these two dispersal strategies are negatively correlated. Our results suggest that negative covariation is widely anticipated from theory. Empirical studies often reported evidence of weak negative covariation, although more complicated patterns were also evident, including across levels of biological organisation. Existing literature has largely focused on plants with dormancy capability, one or two phases of the dispersal process (emigration and/or transfer) and a single level of biological organisation (theory: individual; empirical: species). We highlight patterns of covariation across levels of organisation and conclude with a discussion of the consequences of dispersal through space and time and future research areas that should improve our understanding of dispersal‐related life‐history syndromes.