bluuebunny/crossref_metadata_2025 huggingface dataset:
Diet influences salinity preference of an estuarine fish, the killifishFundulus heteroclitus
Authors: Bucking Carol , Wood Chris M. , Grosell Martin
Published: May 2012

Understanding the interplay among the external environment, physiology and adaptive behaviour is crucial for understanding how animals survive in their natural environments. The external environment can have wide ranging effects on the physiology of animals, while behaviour determines which environments are encountered. Here, we identified changes in the behavioural selection of external salinity in Fundulus heteroclitus, an estuarine teleost, as a consequence of digesting a meal. Fish that consumed high levels of dietary calcium exhibited a higher preferred salinity compared with unfed fish, an effect that was exaggerated by elevated dietary sodium chloride. The mean swimming speed (calculated as a proxy of activity level) was not affected by consuming a diet of any type. Constraining fish to water of 22 p.p.t. salinity during the digestion of a meal did not alter the amount of calcium that was absorbed across the intestine. However, when denied the capacity to increase their surrounding salinity, the compromised ability to excrete calcium to the water resulted in significantly elevated plasma calcium levels, a potentially hazardous physiological consequence. This study is the first to show that fish behaviourally exploit their surroundings to enhance their ionoregulation during digestion, and to pinpoint the novel role of dietary calcium and sodium in shaping this behaviour. We conclude that in order to resolve physiological disturbances in ion balance created by digestion, fish actively sense and select the environment they inhabit. Ultimately, this may result in transient diet-dependent alteration of the ecological niches occupied by fishes, with broad implications for both physiology and ecology.
Leaf beetle attachment on wrinkles: isotropic friction on anisotropic surfaces
Authors: Voigt Dagmar , Schweikart Alexandra , Fery Andreas , Gorb Stanislav
Published: May 2012

The influence of surface roughness on the attachment ability of insects has been repeatedly reported. In previous experiments, complex surface topographies were used as test substrates, whereas periodical structures have so far been neglected. In the present study, traction experiments with adult beetles Gastrophysa viridula and Leptinotarsa decemlineata were carried out to study the influence of surfaces, structured with periodical wrinkles, on insect attachment. Force measurements were carried out on male and female insects, both intact and after removal of claws, performing tethered walking on five polydimethylsiloxane substrates: (i) smooth, non-structured (control), (ii–v) structured with wrinkles of different wavelengths (366, 502, 911 and 25,076 nm). In two test series, beetles walked either perpendicular or parallel to the wrinkle alignment. Adults of G. viridula produced generally higher forces than those of L. decemlineata. The results show that the alignment of wrinkles had no significant influence on the force generation by beetles, probably because of the skewed position of their tarsomeres relative to the substrates. In both sexes, the highest force values were obtained on surfaces with wrinkles of 25 μm wavelength. On other wrinkled substrates, forces were significantly reduced in both males and females compared with the smooth, flat control, with the minimum force achieved on wrinkles with a wavelength of 911 nm.
Is reproduction costly? No increase of oxidative damage in breeding bank voles
Authors: Ołdakowski Łukasz , Piotrowska Żaneta , Chrząścik Katarzyna M. , Sadowska Edyta T. , Koteja Paweł , Taylor Jan R. E.
Published: May 2012

According to life-history theory, investment in reproduction is associated with costs, which should appear as decreased survival to the next reproduction or lower future reproductive success. It has been suggested that oxidative stress may be the proximate mechanism of these trade-offs. Despite numerous studies of the defense against reactive oxygen species (ROS) during reproduction, very little is known about the damage caused by ROS to the tissues of wild breeding animals. We measured oxidative damage to lipids and proteins in breeding bank vole (Myodes glareolus) females after rearing one and two litters, and in non-breeding females. We used bank voles from lines selected for high maximum aerobic metabolic rates (which also had high resting metabolic rates and food intake) and non-selected control lines. The oxidative damage was determined in heart, kidneys and skeletal muscles by measuring the concentration of thiobarbituric acid-reactive substances, as markers of lipid peroxidation, and carbonyl groups in proteins, as markers of protein oxidation. Surprisingly, we found that the oxidative damage to lipids in kidneys and muscles was actually lower in breeding than in non-breeding voles, and it did not differ between animals from the selected and control lines. Thus, contrary to our predictions, females that bred suffered lower levels of oxidative stress than those that did not reproduce. Elevated production of antioxidant enzymes and the protective role of sex hormones may explain the results. The results of the present study do not support the hypothesis that oxidative damage to tissues is the proximate mechanism of reproduction costs.
Getting around when you’re round: quantitative analysis of the locomotion of the blunt-spined brittle star,Ophiocoma echinata
Authors: Astley Henry C.
Published: May 2012

Brittle stars (Ophiuroidea, Echinodermata) are pentaradially symmetrical echinoderms that use five multi-jointed limbs to locomote along the seafloor. Prior qualitative descriptions have claimed coordinated movements of the limbs in a manner similar to tetrapod vertebrates, but this has not been evaluated quantitatively. It is uncertain whether the ring-shaped nervous system, which lacks an anatomically defined anterior, is capable of generating rhythmic coordinated movements of multiple limbs. This study tested whether brittle stars possess distinct locomotor modes with strong inter-limb coordination as seen in limbed animals in other phyla (e.g. tetrapods and arthropods), or instead move each limb independently according to local sensory feedback. Limb tips and the body disk were digitized for 56 cycles from 13 individuals moving across sand. Despite their pentaradial anatomy, all individuals were functionally bilateral, moving along the axis of a central limb via synchronous motions of contralateral limbs (±∼13% phase lag). Two locomotor modes were observed, distinguishable mainly by whether the central limb was directed forwards or backwards. Turning was accomplished without rotation of the body disk by defining a different limb as the center limb and shifting other limb identities correspondingly, and then continuing locomotion in the direction of the newly defined anterior. These observations support the hypothesis that, in spite of their radial body plan, brittle stars employ coordinated, bilaterally symmetrical locomotion.
Respiratory properties of blood in the harbor porpoise,Phocoena phocoena
Authors: Soegaard Lisette B. , Hansen Marie N. , van Elk Cornelis , Brahm Jesper , Jensen Frank B.
Published: May 2012

Harbor porpoises are active divers that exchange O2 and CO2 with the environment during a fast single breath upon surfacing. We investigated blood O2-transporting properties, buffer characteristics, Cl– transport via the erythrocyte anion exchanger (AE1), circulating nitric oxide metabolites and hemoglobin nitrite reduction in harbor porpoises with the aim to evaluate traits that are adaptive for diving behavior. Blood O2 affinity was higher in harbor porpoises than in similar sized terrestrial mammals, as supported by our parallel recordings of O2 equilibria in sheep and pig blood. Further, O2 affinity tended to increase with increasing body mass. A high O2 affinity favors O2 extraction from the lungs, but a normal Bohr effect (ΔlogP50/ΔpH=–0.46) gradually lowers O2 affinity during dives (where CO2 accumulates) to assist O2 off-loading to perfused tissues. The true plasma non-bicarbonate buffer value was moderately higher than in terrestrial mammals and increased upon deoxygenation. Plasma bicarbonate was also relatively high, contributing to increase the overall buffer capacity. The apparent Cl– permeability of harbor porpoise erythrocytes was similar to the human value at 37°C, showing absence of a comparative increase in the velocity of erythrocyte HCO –3/Cl– exchange to aid CO2 excretion. The Q10 for AE1-mediated Cl– transport in harbor porpoises was lower than in humans and seemed to match the Q10 for metabolism (Q10≈2). Plasma nitrite, plasma nitrate and hemoglobin-mediated nitrite reduction were elevated compared with mammalian standards, suggesting that increased nitric oxide bioavailability and nitrite-derived nitric oxide could play important roles in diving physiology.
Characterization of extended co-culture of non-typeable Haemophilus influenzae with primary human respiratory tissues
Authors: Ren Dabin , Nelson Kevin L , Uchakin Peter N , Smith Arnold L , Gu Xin-Xing , Daines Dayle A
Published: May 2012

Non-typeable Haemophilus influenzae (NTHi) are human-adapted Gram-negative bacteria that comprise part of the normal flora of the human upper airway, but are also responsible for a number of mucosal infections such as otitis media and bronchitis. These infections often recur and can become chronic. To characterize the effect of long-term co-culture of NTHi with human tissues, we infected primary respiratory epithelial cells grown at the air–liquid interface with three NTHi strains over a range of 1–10 days. Scanning and transmission electron microscopy of tissues confirmed that intact NTHi were persisting paracellularly, while organisms observed in intracellular vacuoles appeared degraded. Furthermore, the apical surface and tight junctions of the infected tissues were undisturbed, with high transepithelial electrical resistances, while the basal cell layer displayed more junctional disorganization and wider intercellular spaces than the uninfected control tissues. Although the tissues elaborated the cytokine profile reported for NTHi-caused otitis media in vivo, there was little change in the dynamics of cytokine secretion over the time points tested. Finally, we report that NTHi strains released outer membrane vesicles (OMVs) during extended co-culture with the tissues, and show that these OMVs directly interact with host cell membranes.
From Right Place - Wrong Person, to Right Place - Right Person: Dignified Care for Older People
Authors: Tadd Win , Hillman Alex , Calnan Michael , Calnan Sian , Read Simon , Bayer Antony
Published: May 2012

Objectives

To examine: older people's and their relatives' views of dignified care; health care practitioners' behaviours and practices in relation to dignified care; the occupational, organizational and cultural factors that impact on care; and develop evidence-based recommendations for dignified care.

Methods

An ethnography of four acute trusts in England and Wales involving semi-structured interviews with recently discharged older people (n = 40), their relatives (n = 25), frontline staff (n = 79) and Trust managers (n = 32), complemented by 617 hours of non-participant observation in 16 wards in NHS trusts.

Results

‘Right Place - Wrong Person’ refers to the staffs' belief that acute wards are not the ‘right place’ for older people. Wards were poorly-designed, confusing and inaccessible for older people; older people were bored through lack of communal spaces and activities and they expressed concern about the close proximity of patients of the opposite sex; staff were demoralised and ill-equipped with skills and knowledge to care for older people, and organizational priorities caused patients to be frequently moved within the system. In none of the wards studied was care either totally dignified or totally undignified. Variations occurred from ward to ward, in the same ward when different staff were on-duty and at different times of the day.

Conclusions

The failure to provide dignified care is often a result of systemic and organizational factors rather than a failure of individual staff and it is these that must be addressed if dignified care is to be ensured.
Socioeconomic Differences in Case Finding Among General Practices in England: Analysis of Secondary Data
Authors: Dixon Anna , Khachatryan Artak , Tian Yang
Published: May 2012

Objectives

To determine how levels of case finding differ between general practices in England by level of population socioeconomic deprivation.

Method

Observational analysis of data from the Quality and Outcome Framework in England for 2005/06. It covered 8339 primary care practices. Reported prevalence and estimated prevalence for coronary heart disease, chronic obstructive pulmonary disease, stroke and hypertension were compared.

Results

The gap between estimated and reported prevalence increased with population deprivation and was higher among practices in more deprived areas (defined as Spearhead areas) for all four conditions after adjustment for practice level variables.

Conclusions

There is some evidence of unmet need in areas of social deprivation. Existing financial incentives in the Quality and Outcome Framework may be insufficient to promote active case finding by practices serving deprived populations.
Use of Orlistat 60 mg in the Management of Weight Loss before Bariatric Surgery
Authors: Malone Margaret , Alger-Mayer Sharon A , Lindstrom Jennifer
Published: May 2012

BACKGROUND:

Patients undergoing gastric bypass surgery are usually required to lose weight during the preoperative phase of their management. For some individuals, this is difficult to achieve with diet and exercise alone, and the use of weight loss medication may be considered a treatment option.

OBJECTIVE:

To evaluate the use of orlistat 60 mg taken up to 3 times daily as an adjunct to achieve the 10% preoperative weight loss recommended in this bariatric program prior to gastric bypass surgery.

METHODS:

The aim was to recruit 50 patients (25 treatment, 25 controls) who were in the preoperative phase of their bariatric program. Patients were referred by their physician. Control subjects were selected from individuals who were eligible but not interested in participating in the study during the same period. All patients received usual care.

RESULTS:

Nineteen patients (5 males) and 19 age- and sex-matched controls were included. The mean (SD) initial body mass index for the treatment versus control group was, respectively, 49.5 (10.5) versus 47.2 (4.9) kg/m2 (p = 0.559). At 3 months, the percent excess weight (EW) loss was 2.4 (3.8) (n = 15) versus 5.5 (7.6) (n = 19) (p = 0.111) and the percent total body weight (TBW) loss was 1.2 (1.9) versus 2.9 (4.1) (p = 0.103). At 6 months, the percent EW loss was 3.6 (6.4) (n = 9) versus 10.2 (8.0) (n = 16) (p = 0.036) and the percent TBW loss was 2.0 (3.4) versus 5.4 (4.2) (p = 0.048).

CONCLUSIONS:

Some patients felt that orlistat was beneficial for weight loss; however, overall, they did not show benefit from its addition to their preoperative weight loss management.
A Polypill for All? Critical Review of the Polypill Literature for Primary Prevention of Cardiovascular Disease and Stroke
Authors: Carey Katherine M , Cornee Morgan R , Donovan Jennifer L , Kanaan Abir O
Published: May 2012

Objective:

To evaluate the efficacy and safety of the polypill for prevention of cardiovascular disease (CVD) and stroke and to present literature related to the polypill components (statin, aspirin, antihypertensive) for primary prevention of CVD and stroke.

Data Sources:

A literature search was conducted in MEDLINE (1948-January 2011) and EMBASE (1974-January 2011) using the terms polypill and Polycap. When limited to clinical trials, systematic reviews, or meta-analyses, 7 studies were identified. Bibliographies of pertinent review articles and studies were scanned for additional references. A similar search was conducted to identify literature related to the use of polypill components for primary prevention of CVD and stroke.

Study Selection and Data Extraction:

Studies that evaluated the hypothetical benefits of a polypill and controlled trials that assessed a formulation of the polypill related to prevention of CVD and stroke were included. Studies were assessed for efficacy, safety, drug interactions, and clinical pharmacokinetics.

Data Synthesis:

An initial study to predict benefit estimated that a hypothetical polypill would reduce diastolic blood pressure by 11 mm Hg and low-density lipoprotein cholesterol (LDL-C) by 70 mg/dL, thus reducing the relative risks of CVD and stroke by 68% and 80%, respectively. One clinical trial in patients at low risk for CVD and stroke found that diastolic Wood pressure was reduced by 1.6 mm Hg and LDL-C was reduced by 17.7 mg/dL, correlating with 44% and 21% reduction in the relative risks of CVD and stroke, respectively. Studies in higher risk patients reported reductions in systolic blood pressure of up to 28.8 mm Hg and in LDL-C of up to 54 mg/dL, correlating with 62% and 60% relative reduction in risks of CVD and stroke, respectively.

Conclusions:

Polypill study results have been more modest than originally theorized. However, results show promise in patients at higher risk for CVD and stroke.
Use of Aspirin and Clopidogrel After Coronary Artery Bypass Graft Surgery
Authors: Leon Noelle de , Jackevicius Cynthia A
Published: May 2012

Objective:

To evaluate the evidence for the use of dual antiplatelet therapy (DAPT) with aspirin and Clopidogrel following coronary artery bypass graft (CABG) surgery.

Data Sources:

Literature was accessed through PubMed (1950-November 2011), EMBASE (1976-November 2011), and the Cochrane databases using the terms Clopidogrel and coronary artery bypass graft. Citations from available articles were used for additional references and ClinicalTrials.gov was accessed for abstracts of ongoing studies.

Study Selection Ano Data Extraction:

Peer-reviewed studies that evaluated DAPT use after CABQ surgery in adult humans were assessed for inclusion.

Data Synthesis:

Four randomized clinical trials evaluating surrogate end points and 9 studies (3 subgroup analyses, 6 observational) evaluating clinical outcomes were reviewed. Three clinical trials assessing surrogate end points failed to demonstrate an improvement in graft patency with DAPT use, while 1 clinical trial found an increase in graft patency. As for clinical outcomes, 1 subgroup analysis demonstrated that the benefit of DAPT post-CABG after a non-ST-elevation acute coronary syndrome diminished following surgery, while an observational study demonstrated a trend toward decreased mortality. In post-CABG patients who did not experience acute coronary syndrome, 2 subgroup analyses proved inconclusive and an observational study found DAPT use to be associated with reducing in-hospital mortality, while another observational study was not associated with reduced long-term mortality. Three observational studies in off-pump CABG patients showed that DAPT use was feasible.

Conclusions:

Evidence for DAPT use following CABG is limited to subgroup analyses, observational studies, and trials with surrogate end points. The majority of clinical trials have failed to demonstrate an improvement in graft patency with DAPT. Current evidence does not support the use of DAPT to improve graft patency, and more evidence from randomized controlled trials assessing clinical outcomes is necessary to make definitive recommendations.
Measuring The Social Opportunity Cost of Labor In Mexico
Authors: Guillermo-Peon Sylvia B. , Harberger Arnold C.
Published: May 2012

This paper reviews the theory underlying the concept of the social opportunity cost of labor (SOCL), as that concept is used in benefit-cost analysis and in applied welfare economics generally. It then presents in detail the procedures to be followed in estimating the SOCL in real-world cases. Important steps in data processing include calculating gross and net wages from data on “reported” wages. Further economic analysis involves taking account of migration patterns and of labor market duality. Estimates are made for 32 labor market areas in Mexico, covering 21 occupations for males and 19 for females.

Our main results are a) that there are important differences between reported wages and the gross wages paid by employers, and also between both of these and the net wages received by workers, and b) that taking labor market duality into account leads to significant modifications of our SOCL estimates. More important, perhaps, than our specific estimates for Mexico, is the methodological framework that we use. This framework, based on the fundamental principles of applied welfare economics, can serve as a useful starting point for serious estimation of the SOCL for other countries.
Performance Comparison of
Coherent Time-spreading and Spectral Phase
Encoding OCDMA Systems
Authors: Chen Xiaogang , Huang Dexiu
Published: May 2012

We compared the
bit-error-rate (BER) and throughput
performance of coherent time-spreading (TS)
and spectral phase encoding (SPE) optical code
division multiple access (OCDMA) systems. The
results indicate that for the short input
pulse (250–300 fs pulsewidth),
SPE-OCDMA can in principle yield a substantial
throughput advantage over TS-OCDMA
systems.
Zirconium in the Nuclear Industry: 16th International Symposium
Authors: Limbäck Magnus , Barbéris Pierre
Published: May 2012

Description

Forty-two peer-reviewed papers cover the entire spectrum of zirconium metallurgy, from basic metallurgy to accidental conditions and transport, through fabrication, creep and growth, and corrosion and hydriding.

Sections cover
Dynamic Changes in Interneuron Morphophysiological Properties Mark the Maturation of Hippocampal Network Activity
Authors: Allene Camille , Picardo Michel A. , Becq Hélène , Miyoshi Goichi , Fishell Gord , Cossart Rosa
Published: May 2012

During early postnatal development, neuronal networks successively produce various forms of spontaneous patterned activity that provide key signals for circuit maturation. Initially, in both rodent hippocampus and neocortex, coordinated activity emerges in the form of synchronous plateau assemblies (SPAs) that are initiated by sparse groups of gap-junction-coupled oscillating neurons. Subsequently, SPAs are replaced by synapse-driven giant depolarizing potentials (GDPs). Whether these sequential changes in mechanistically distinct network activities correlate with modifications in single-cell properties is unknown. To determine this, we studied the morphophysiological fate of single SPA cells as a function of development. We focused on CA3 GABAergic interneurons, which are centrally involved in generating GDPs in the hippocampus. As the network matures, GABAergic neurons are engaged more in GDPs and less in SPAs. Using inducible genetic fate mapping, we show that the individual involvement of GABAergic neurons in SPAs is correlated to their temporal origin. In addition, we demonstrate that the SPA-to-GDP transition is paralleled by a remarkable maturation in the morphophysiological properties of GABAergic neurons. Compared with those involved in GDPs, interneurons participating in SPAs possess immature intrinsic properties, receive synaptic inputs spanning a wide amplitude range, and display large somata as well as membrane protrusions. Thus, a developmental switch in the morphophysiological properties of GABAergic interneurons as they progress from SPAs to GDPs marks the emergence of synapse-driven network oscillations.
Directional Neuronal Migration Is Impaired in Mice Lacking Adenomatous Polyposis Coli 2
Authors: Shintani Takafumi , Takeuchi Yasushi , Fujikawa Akihiro , Noda Masaharu
Published: May 2012

Adenomatous polyposis coli 2 (APC2) is a family member of APC and mainly expressed in the nervous system. We previously reported that APC2 plays a critical role in axonal projection through the regulation of microtubule stability. Here, we show that a lack ofApc2induces severe laminary defects in some regions of the mouse brain, including the cerebral cortex and cerebellum.In vivoBrdU labeling and immunohistochemical analyses with specific markers revealed that the laminary abnormalities are a result of dysregulated neuronal migration by a cell-autonomous mechanism. Using total internal reflection fluorescent microscopy, we found that APC2 is distributed along actin fibers as well as microtubules. Cerebellar granule cells in dissociated cultures andin vivoshowed that BDNF-stimulated directional migration is impaired inApc2-deficient neurons. We revealed that this impairment stems from the dysregulations of Rho family GTPase activation and TrkB localization, which disrupts the formation of BDNF-stimulated F-actin at the leading edge. Thus, APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals.
β-Amyloid Inhibits Protein Prenylation and Induces Cholesterol Sequestration by Impairing SREBP-2 Cleavage
Authors: Mohamed Amany , Saavedra Lucila , Di Pardo Alba , Sipione Simonetta , Posse de Chaves Elena
Published: May 2012

Accumulation of β-amyloid (Aβ) inside brain neurons is an early and crucial event in Alzheimer's disease (AD). Studies in brains of AD patients and mice models of AD suggested that cholesterol homeostasis is altered in neurons that accumulate Aβ. Here we directly investigated the role of intracellular oligomeric Aβ42(oAβ42) in neuronal cholesterol homeostasis. We report that oAβ42induces cholesterol sequestration without increasing cellular cholesterol mass. Several features of AD, such as endosomal abnormalities, brain accumulation of Aβ and neurofibrillary tangles, and influence of apolipoprotein E genotype, are also present in Niemann-Pick type C, a disease characterized by impairment of intracellular cholesterol trafficking. These common features and data presented here suggest that a pathological mechanism involving abnormal cholesterol trafficking could take place in AD. Cholesterol sequestration in Aβ-treated neurons results from impairment of intracellular cholesterol trafficking secondary to inhibition of protein prenylation. oAβ42reduces sterol regulatory element-binding protein-2 (SREBP-2) cleavage, causing decrease of protein prenylation. Inhibition of protein prenylation represents a mechanism of oAβ42-induced neuronal death. Supply of the isoprenoid geranylgeranyl pyrophosphate to oAβ42-treated neurons recovers normal protein prenylation, reduces cholesterol sequestration, and prevents Aβ-induced neurotoxicity. Significant to AD, reduced levels of protein prenylation are present in the cerebral cortex of the TgCRND8 mouse model. In conclusion, we demonstrate a significant inhibitory effect of Aβ on protein prenylation and identify SREBP-2 as a target of oAβ42, directly linking Aβ to cholesterol homeostasis impairment.
Transglutaminase Inhibition Protects against Oxidative Stress-Induced Neuronal Death Downstream of Pathological ERK Activation
Authors: Basso Manuela , Berlin Jill , Xia Li , Sleiman Sama F. , Ko Brendan , Haskew-Layton Renee , Kim Eunhee , Antonyak Marc A. , Cerione Richard A. , Iismaa Siiri E. , Willis Dianna , Cho Sunghee , Ratan Rajiv R.
Published: May 2012

Molecular deletion of transglutaminase 2 (TG2) has been shown to improve function and survival in a host of neurological conditions including stroke, Huntington's disease, and Parkinson's disease. However, unifying schemes by which these cross-linking or polyaminating enzymes participate broadly in neuronal death have yet to be presented. Unexpectedly, we found that in addition to TG2, TG1 gene expression level is significantly induced following strokein vivoor due to oxidative stressin vitro. Forced expression of TG1 or TG2 proteins is sufficient to induce neuronal death inRattus norvegicuscortical neuronsin vitro. Accordingly, molecular deletion of TG2 alone is insufficient to protectMus musculusneurons from oxidative death. By contrast, structurally diverse inhibitors used at concentrations that inhibit TG1 and TG2 simultaneously are neuroprotective. These small molecules inhibit increases in neuronal transamidating activity induced by oxidative stress; they also protect neurons downstream of pathological ERK activation when added well after the onset of the death stimulus. Together, these studies suggest that multiple TG isoforms, not only TG2, participate in oxidative stress-induced cell death signaling; and that isoform nonselective inhibitors of TG will be most efficacious in combating oxidative death in neurological disorders.
Differential Connectivity of Perirhinal and Parahippocampal Cortices within Human Hippocampal Subregions Revealed by High-Resolution Functional Imaging
Authors: Libby Laura A. , Ekstrom Arne D. , Ragland J. Daniel , Ranganath Charan
Published: May 2012

Numerous studies support the importance of the perirhinal cortex (PRC) and parahippocampal cortex (PHC) in episodic memory. Theories of PRC and PHC function in humans have been informed by neuroanatomical studies of these regions obtained in animal tract-tracing studies, but knowledge of the connectivity of PHC and PRC in humans is limited. To address this issue, we used resting-state functional magnetic resonance imaging to compare the intrinsic functional connectivity profiles associated with the PRC and PHC both across the neocortex and within the subfields of the hippocampus. In Experiment 1, we acquired standard-resolution whole-brain resting-state fMRI data in 15 participants, and in Experiment 2, we acquired high-resolution resting-state fMRI data targeting the hippocampus in an independent sample of 15 participants. Experiment 1 revealed that PRC showed preferential connectivity with the anterior hippocampus, whereas PHC showed preferential connectivity with posterior hippocampus. Experiment 2 indicated that this anterior–posterior functional connectivity dissociation was more evident for subfields CA1 and subiculum than for a combined CA2/CA3/dentate gyrus region. Finally, whole-brain analyses from Experiment 1 revealed preferential PRC connectivity with an anterior temporal and frontal cortical network, and preferential PHC connectivity with a posterior medial temporal, parietal, and occipital network. These results suggest a framework for refining models of the functional organization of the human medial temporal lobes in which the PRC and PHC are associated with distinct neocortical pathways that, in turn, may differentially interact with regions along the anterior–posterior axis of the hippocampus.
Olfactory Deficits Cause Anxiety-Like Behaviors in Mice
Authors: Glinka Meredith E. , Samuels Benjamin A. , Diodato Assunta , Teillon Jérémie , Feng Mei Dan , Shykind Benjamin M. , Hen René , Fleischmann Alexander
Published: May 2012

Anxiety disorders are characterized by persistent fear in the absence of immediate threat and represent the most common psychiatric diseases, with an estimated 28% lifetime prevalence worldwide (Kessler et al., 2010). While symptoms of anxiety are typically evoked by sensory stimuli, it is unknown whether sensory deficits contribute to the development of anxiety disorders. Here we examine the effect of defined genetic mutations that compromise the function of the olfactory system on the development of anxiety-like behaviors in mice. We show that the functional inactivation of the main olfactory epithelium, but not the vomeronasal organ, causes elevated levels of anxiety. Anxiety-like behaviors are also observed in mice with a monoclonal nose, that are able to detect and discriminate odors but in which the patterns of odor-evoked neural activity are perturbed. In these mice, plasma corticosterone levels are elevated, suggesting that olfactory deficits can lead to chronic stress. These results demonstrate a central role for olfactory sensory cues in modulating anxiety in mice.
Differential Modulation of the Oligodendrocyte Transcriptome by Sonic Hedgehog and Bone Morphogenetic Protein 4 via Opposing Effects on Histone Acetylation
Authors: Wu Muzhou , Hernandez Marylens , Shen Siming , Sabo Jennifer K. , Kelkar Dipti , Wang Ju , O'Leary Robert , Phillips Greg R. , Cate Holly S. , Casaccia Patrizia
Published: May 2012

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is regulated by the interplay between extrinsic signals and intrinsic epigenetic determinants. In this study, we analyze the effect that the extracellular ligands sonic hedgehog (Shh) and bone morphogenetic protein 4 (BMP4), have on histone acetylation and gene expression in cultured OPCs. Shh treatment favored the progression toward oligodendrocytes by decreasing histone acetylation and inducing peripheral chromatin condensation. BMP4 treatment, in contrast, inhibited the progression toward oligodendrocytes and favored astrogliogenesis by favoring global histone acetylation and retaining euchromatin. Pharmacological treatment or silencing of histone deacetylase 1 (Hdac1) or histone deacetylase 2 (Hdac2) in OPCs did not affect BMP4-dependent astrogliogenesis, while it prevented Shh-induced oligodendrocyte differentiation and favored the expression of astrocytic genes. Transcriptional profiling of treated OPCs, revealed that BMP4-inhibition of oligodendrocyte differentiation was accompanied by increased levels of Wnt (Tbx3) and Notch-target genes (Jag1,Hes1,Hes5,Hey1, andHey2), decreased recruitment of Hdac and increased histone acetylation at these loci. Similar upregulation of Notch-target genes and increased histone acetylation were observed in the corpus callosum of mice infused with BMP4 during cuprizone-induced demyelination. We conclude that Shh and Bmp4 differentially regulate histone acetylation and chromatin structure in OPCs and that BMP4 acts as a potent inducer of gene expression, including Notch and Wnt target genes, thereby enhancing the crosstalk among signaling pathways that are known to inhibit myelination and repair.
LMTK1/AATYK1 Is a Novel Regulator of Axonal Outgrowth That Acts via Rab11 in a Cdk5-Dependent Manner
Authors: Takano Tetsuya , Tomomura Mineko , Yoshioka Nozomu , Tsutsumi Koji , Terasawa Yukichi , Saito Taro , Kawano Hitoshi , Kamiguchi Hiroyuki , Fukuda Mitsunori , Hisanaga Shin-ichi
Published: May 2012

Axonal outgrowth is a coordinated process of cytoskeletal dynamics and membrane trafficking; however, little is known about proteins responsible for regulating the membrane supply. LMTK1 (lemur kinase 1)/AATYK1 (apoptosis-associated tyrosine kinase 1) is a serine/threonine kinase that is highly expressed in neurons. We recently reported that LMTK1 plays a role in recycling endosomal trafficking in CHO-K1 cells. Here we explore the role of LMTK1 in axonal outgrowth and its regulation by Cdk5 using mouse brain cortical neurons. LMTK1 was expressed and was phosphorylated at Ser34, the Cdk5 phosphorylation site, at the time of axonal outgrowth in culture and colocalized with Rab11A, the small GTPase that regulates recycling endosome traffic, at the perinuclear region and in the axon. Overexpression of the unphosphorylated mutant LMTK1-S34A dramatically promoted axonal outgrowth in cultured neurons. Enhanced axonal outgrowth was diminished by the inactivation of Rab11A, placing LMTK1 upstream of Rab11A. Unexpectedly, the downregulation of LMTK1 by knockdown or gene targeting also significantly enhanced axonal elongation. Rab11A-positive vesicles were transported anterogradely more quickly in the axons ofLMTK1-deficient neurons than in those of wild-type neurons. The enhanced axonal outgrowth was reversed by LMTK1-WT or the LMTK1-S34D mutant, which mimics the phosphorylated state, but not by LMTK1-S34A. Thus, LMTK1 can negatively control axonal outgrowth by regulating Rab11A activity in a Cdk5-dependent manner, and Cdk5–LMTK1–Rab11 is a novel signaling pathway involved in axonal outgrowth.
Comparative Impact of Voltage-Gated Calcium Channels and NMDA Receptors on Mitochondria-Mediated Neuronal Injury
Authors: Stanika Ruslan I. , Villanueva Idalis , Kazanina Galina , Andrews S. Brian , Pivovarova Natalia B.
Published: May 2012

Glutamate excitotoxicity, a major component of many neurodegenerative disorders, is characterized by excessive calcium influx selectively through NMDARs. However, there is a substantial uncertainty concerning why other known routes of significant calcium entry, in particular, VGCCs, are not similarly toxic. Here, we report that in the majority of neurons in rat hippocampal and cortical cultures, maximal L-type VGCC activation induces much lower calcium loading than toxic NMDAR activation. Consequently, few depolarization-activated neurons exhibit calcium deregulation and cell death. Activation of alternative routes of calcium entry induced neuronal death in proportion to the degree of calcium loading. In a small subset of neurons, depolarization evoked stronger calcium elevations, approaching those induced by toxic NMDA. These neurons were characterized by elevated expression of VGCCs and enhanced voltage-gated calcium currents, mitochondrial dysfunction and cell death. Preventing VGCC-dependent mitochondrial calcium loading resulted in stronger cytoplasmic calcium elevations, whereas inhibiting mitochondrial calcium clearance accelerated mitochondrial depolarization. Both observations further implicate mitochondrial dysfunction in VGCC-mediated cell death. Results indicate that neuronal vulnerability tracks the extent of calcium loading but does not appear to depend explicitly on the route of calcium entry.
Reduced Excitatory Neurotransmission and Mild Autism-Relevant Phenotypes in AdolescentShank3Null Mutant Mice
Authors: Yang Mu , Bozdagi Ozlem , Scattoni Maria Luisa , Wöhr Markus , Roullet Florence I. , Katz Adam M. , Abrams Danielle N. , Kalikhman David , Simon Harrison , Woldeyohannes Leuk , Zhang James Y. , Harris Mark J. , Saxena Roheeni , Silverman Jill L. , Buxbaum Joseph D. , Crawley Jacqueline N.
Published: May 2012

Mutations in the synaptic scaffolding protein geneSHANK3are strongly implicated in autism and Phelan–McDermid 22q13 deletion syndrome. The precise location of the mutation within theShank3gene is key to its phenotypic outcomes. Here, we report the physiological and behavioral consequences of null and heterozygous mutations in the ankyrin repeat domain inShank3mice. Both homozygous and heterozygous mice showed reduced glutamatergic transmission and long-term potentiation in the hippocampus with more severe deficits detected in the homozygous mice. Three independent cohorts were evaluated for magnitude and replicability of behavioral endophenotypes relevant to autism and Phelan–McDermid syndrome. Mild social impairments were detected, primarily in juveniles during reciprocal interactions, while all genotypes displayed normal adult sociability on the three-chambered task. Impaired novel object recognition and rotarod performance were consistent across cohorts of null mutants. Repetitive self-grooming, reduced ultrasonic vocalizations, and deficits in reversal of water maze learning were detected only in some cohorts, emphasizing the importance of replication analyses. These results demonstrate the exquisite specificity of deletions in discrete domains within theShank3gene in determining severity of symptoms.
Synaptic NMDA Receptors Mediate Hypoxic Excitotoxic Death
Authors: Wroge Christine M. , Hogins Joshua , Eisenman Larry , Mennerick Steven
Published: May 2012

Excessive NMDA receptor activation and excitotoxicity underlies pathology in many neuropsychiatric and neurological disorders, including hypoxia/ischemia. Thus, the development of effective therapeutics for these disorders demands a complete understanding of NMDA receptor (NMDAR) activation during excitotoxic insults. The extrasynaptic NMDAR hypothesis posits that synaptic NMDARs are neurotrophic/neuroprotective and extrasynaptic NMDARs are neurotoxic. The extrasynaptic hypothesis is built in part on observed selectivity for extrasynaptic receptors of a neuroprotective use-dependent NMDAR channel blocker, memantine. In rat hippocampal neurons, we found that a neuroprotective concentration of memantine shows little selectivity for extrasynaptic NMDARs when all receptors are tonically activated by exogenous glutamate. This led us to test the extrasynaptic NMDAR hypothesis using metabolic challenge, where the source of excitotoxic glutamate buildup may be largely synaptic. Three independent approaches suggest strongly that synaptic receptors participate prominently in hypoxic excitotoxicity. First, block of glutamate transporters with a nonsubstrate antagonist exacerbated rather than prevented damage, consistent with a primarily synaptic source of glutamate. Second, selective, preblock of synaptic NMDARs with a slowly reversible, use-dependent antagonist protected nearly fully against prolonged hypoxic insult. Third, glutamate pyruvate transaminase, which degrades ambient but not synaptic glutamate, did not protect against hypoxia but protected against exogenous glutamate damage. Together, these results suggest that synaptic NMDARs can mediate excitotoxicity, particularly when the glutamate source is synaptic and when synaptic receptor contributions are rigorously defined. Moreover, the results suggest that in some situations therapeutically targeting extrasynaptic receptors may be inappropriate.
Corporate Brand Management Imperatives: Custodianship, Credibility, and Calibration
Authors: Balmer John M.T.
Published: May 2012

Marshaling case study research insights, this article advances our knowledge of the strategic management of corporate brands. Strategic corporate brand management requires commitment to three critically important imperatives: senior management custodianship; the building and maintaining of brand credibility; and the dynamic calibration of seven identities constituting the corporate brand constellation. This article draws on research dating back to the 1990s and is also informed by the identity-based view of corporate brands perspective and by recent scholarship on the AC4ID Test–a strategic, diagnostic, corporate brand management framework.
Corporate Languages and Strategic Agility: Trapped in Your Jargon or Lost in Translation?
Authors: Brannen Mary Yoko , Doz Yves L.
Published: May 2012

While all of us would easily recognize that language matters in the obvious case of different national languages, or in formal strategic communication to employees or stakeholders, the importance of a firm's informal language as an enabler or constraint for growth and strategic agility has not been recognized. Using qualitative data from in-depth empirical comparative studies, this article develops a conceptual framework for diagnosing two types of strategic language traps and their origins commonly encountered by firms as they attempt to enter new business domains as well as in acquisition driven growth and alliances. It proposes solutions for companies to overcome their specific language trap and enable strategic agility.
Tolerating Babel
Authors: Runions Erin
Published: May 2012

D.W. Griffith’s 1916 film Intolerance: Love’s Struggle through the Ages, and Alejandro González Iñárritu’s 2006 film Babel both treat the biblical figure of Babylon/Babel positively and negatively. These films are analyzed for their ambivalence toward Babylon, as it dramatizes and facilitates the tensions between unity and diversity, control and mobility, rights and interest, individual discipline and regularization of the population at work in biopolitical U.S. empire. These films wish to rebuild Babel: they propose cinema as a universal language able to bridge communicative divides and remedy the violence and social control of intolerant empire. In imagining a more tolerant world, they ostensibly value diversity. Yet they want to return to the normative sexual relations of the white heteronormative family. Thus, both films mirror an ambivalence, also found in Genesis 11, toward social/political unity and diversity, producing a liberal tolerance discourse wherein the regulation and regularization of populations via biopolitics can be detested and yet pursued.
Not-So-Sacred Quests
Authors: Love Mark Cameron
Published: May 2012

While many video games are replete with religious images and intertextuality, the role and purpose of religion and religious intertextuality in video games has not been extensively examined. In this article, I list some occurrences of religion in a variety of video game genres and reflect on the functions religion and religious intertextuality perform in video games. I then proceed to closely play a video game, Bethesda Softworks The Elder Scrolls IV: Oblivion, to examine the roles religion plays in one video game. I conclude that religion in video games operates in a multitude of ways. The most intriguing role it plays is cultural critique as it challenges the close player to reflect on her/his identity and attitudes by demanding the player to ethically evaluate her/his actions in the game world and how they relate to the real world.
Religion is Playing Games
Authors: Plate S Brent
Published: May 2012

Humans are game players. Such a designation began long before video games, but has taken on new significance in light of present technological advances. Video games extend the designations of what it means to be “homo ludens,” and thus what it means to be both human and religious. Studies of video games often take account of the religious content of games, but it is the experiential nature of playing games that extends the argument far into the past and into the future. This article makes an argument that religion, particularly in its ritual form, can be seen through a dialectical relation between the structures of games, and the freedom experienced by players. This is ultimately argued by attention to two different designations of video game varieties: god games and purposeless games.
Three Midwinter Celebrations
Authors: Wilbush Joel
Published: May 2012

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The Enlightenment and the Nineteenth Century, by James C. Livingston, Second Edition. Vol. 1 of Modern Christian Thought and The Twentieth Century, Second Edition. by James C. Livingston and Francis Schüssler Fiorenza, with Sarah Coakley and James H. Evans Jr. Vol. 2 of Modern Christian Thought
Authors: Stewart Adam
Published: May 2012

The Enlightenment and the Nineteenth Century, by James C. Livingston, Second Edition. Vol. 1 of Modern Christian Thought. Fortress Press, 2006. xv + 430pp., pbk $35.00. ISBN-13: 9780800637958.
The Twentieth Century, Second Edition. by James C. Livingston and Francis Schüssler Fiorenza, with Sarah Coakley and James H. Evans Jr. Vol. 2 of Modern Christian Thought. Fortress Press, 2006. xvi + 544pp., pbk $35.00 ISBN-13: 9780800637965.
The Hebrew Bible: A Comparative Approach, by Christopher D. Stanley
Authors: Linville James
Published: May 2012

The Hebrew Bible: A Comparative Approach, by Christopher D. Stanley. Fortress Press, 2010. 560pp., pbk. US$42.00. ISBN-13 978-0800663476
Second Strings and Linguistic Connections: Bilingual and Bilinguistic Explorations. An Introduction.
Authors: Gardner-Chloros Penelope
Published: May 2012

The conference from which these papers arise was held at Birkbeck, University of London, on 5/6 November 2008 in honour of Michel Blanc’s election to a Fellowship at Birkbeck. As is appropriate for a set of papers dedicated to the author of Bilinguality and Bilingualism (1989), the contributions to this issue cover a wide range from bilinguality (issues affecting the individual) to bilingualism (issues affecting groups and societies). The authors have all been associated with the Department of Applied Linguistics (now called ‘Applied Linguistics and Communication’) at some point in its history, some having been colleagues or students of Michel’s and others having worked there after his retirement.