bluuebunny/crossref_metadata_2025 huggingface dataset:
ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting
Authors: Humbert Melissa C. , Weihbrecht Katie , Searby Charles C. , Li Yalan , Pope Robert M. , Sheffield Val C. , Seo Seongjin
Published: November 2012

Mutations affecting ciliary components cause a series of related genetic disorders in humans, including nephronophthisis (NPHP), Joubert syndrome (JBTS), Meckel-Gruber syndrome (MKS), and Bardet-Biedl syndrome (BBS), which are collectively termed “ciliopathies.” Recent protein–protein interaction studies combined with genetic analyses revealed that ciliopathy-related proteins form several functional networks/modules that build and maintain the primary cilium. However, the precise function of many ciliopathy-related proteins and the mechanisms by which these proteins are targeted to primary cilia are still not well understood. Here, we describe a protein–protein interaction network of inositol polyphosphate-5-phosphatase E (INPP5E), a prenylated protein associated with JBTS, and its ciliary targeting mechanisms. INPP5E is targeted to the primary cilium through a motif near the C terminus and prenyl-binding protein phosphodiesterase 6D (PDE6D)-dependent mechanisms. Ciliary targeting of INPP5E is facilitated by another JBTS protein, ADP-ribosylation factor-like 13B (ARL13B), but not by ARL2 or ARL3. ARL13B missense mutations that cause JBTS in humans disrupt the ARL13B–INPP5E interaction. We further demonstrate interactions of INPP5E with several ciliary and centrosomal proteins, including a recently identified ciliopathy protein centrosomal protein 164 (CEP164). These findings indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network that is involved in JBTS and NPHP but independent of the ones previously defined by NPHP and MKS proteins.
Molecular response in one-photon absorption via natural thermal light vs. pulsed laser excitation
Authors: Brumer Paul , Shapiro Moshe
Published: November 2012

Photoinduced biological processes occur via one-photon absorption in natural light, which is weak, continuous wave, and incoherent, but are often studied in the laboratory using pulsed coherent light. Here, we compare the response of a molecule to these two very different sources within a quantized radiation field picture. The latter is shown to induce coherent time evolution in the molecule, whereas the former does not. As a result, the coherent time dependence observed in the laboratory experiments will not be relevant to the natural biological process. Emphasis is placed on resolving confusions regarding this issue that are shown to arise from aspects of quantum measurement and from a lack of appreciation of the proper description of the absorbed photon.
Injectable preformed scaffolds with shape-memory properties
Authors: Bencherif Sidi A. , Sands R. Warren , Bhatta Deen , Arany Praveen , Verbeke Catia S. , Edwards David A. , Mooney David J.
Published: November 2012

Injectable biomaterials are increasingly being explored to minimize risks and complications associated with surgical implantation. We describe a strategy for delivery via conventional needle–syringe injection of large preformed macroporous scaffolds with well-defined properties. Injectable 3D scaffolds, in the form of elastic sponge-like matrices, were prepared by environmentally friendly cryotropic gelation of a naturally sourced polymer. Cryogels with shape-memory properties may be molded to a variety of shapes and sizes, and may be optionally loaded with therapeutic agents or cells. These scaffolds have the capability to withstand reversible deformations at over 90% strain level, and a rapid volumetric recovery allows the structurally defined scaffolds to be injected through a small-bore needle with nearly complete geometric restoration once delivered. These gels demonstrated long-term release of biomolecules in vivo. Furthermore, cryogels impregnated with bioluminescent reporter cells provided enhanced survival, higher local retention, and extended engraftment of transplanted cells at the injection site compared with a standard injection technique. These injectable scaffolds show great promise for various biomedical applications, including cell therapies.
Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature
Authors: Mittelman-Smith Melinda A. , Williams Hemalini , Krajewski-Hall Sally J. , McMullen Nathaniel T. , Rance Naomi E.
Published: November 2012

Estrogen withdrawal in menopausal women leads to hot flushes, a syndrome characterized by the episodic activation of heat dissipation effectors. Despite the extraordinary number of individuals affected, the etiology of flushes remains an enigma. Because menopause is accompanied by marked alterations in hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons, we hypothesized that these neurons could contribute to the generation of flushes. To determine if KNDy neurons participate in the regulation of body temperature, we evaluated the thermoregulatory effects of ablating KNDy neurons by injecting a selective toxin for neurokinin-3 expressing neurons [NK
3
-saporin (SAP)] into the rat arcuate nucleus. Remarkably, KNDy neuron ablation consistently reduced tail-skin temperature (T
SKIN
), indicating that KNDy neurons facilitate cutaneous vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation blocked the reduction of T
SKIN
by 17β-estradiol (E
2
), which occurred in the environmental chamber during the light phase, but did not affect the E
2
suppression of T
SKIN
during the dark phase. At the high ambient temperature of 33 °C, the average core temperature (T
CORE
) of ovariectomized (OVX) control rats was significantly elevated, and this value was reduced by E
2
replacement. In contrast, the average T
CORE
of OVX, KNDy-ablated rats was lower than OVX control rats at 33 °C, and not altered by E
2
replacement. These data provide unique evidence that KNDy neurons promote cutaneous vasodilatation and participate in the E
2
modulation of body temperature. Because cutaneous vasodilatation is a cardinal sign of a hot flush, these results support the hypothesis that KNDy neurons could play a role in the generation of flushes.
Reading and doing arithmetic nonconsciously
Authors: Sklar Asael Y. , Levy Nir , Goldstein Ariel , Mandel Roi , Maril Anat , Hassin Ran R.
Published: November 2012

The modal view in the cognitive and neural sciences holds that consciousness is necessary for abstract, symbolic, and rule-following computations. Hence, semantic processing of multiple-word expressions, and performing of abstract mathematical computations, are widely believed to require consciousness. We report a series of experiments in which we show that multiple-word verbal expressions can be processed outside conscious awareness and that multistep, effortful arithmetic equations can be solved unconsciously. All experiments used Continuous Flash Suppression to render stimuli invisible for relatively long durations (up to 2,000 ms). Where appropriate, unawareness was verified using both objective and subjective measures. The results show that novel word combinations, in the form of expressions that contain semantic violations, become conscious before expressions that do not contain semantic violations, that the more negative a verbal expression is, the more quickly it becomes conscious, and that subliminal arithmetic equations prime their results. These findings call for a significant update of our view of conscious and unconscious processes.
Bidirectional influence of sodium channel activation on NMDA receptor–dependent cerebrocortical neuron structural plasticity
Authors: George Joju , Baden Daniel G. , Gerwick William H. , Murray Thomas F.
Published: November 2012

Neuronal activity regulates brain development and synaptic plasticity through
N
-methyl-
d
-aspartate receptors (NMDARs) and calcium-dependent signaling pathways. Intracellular sodium ([Na
+
]
i
) also exerts a regulatory influence on NMDAR channel activity, and [Na
+
]
i
may, therefore, function as a signaling molecule. In an attempt to mimic the influence of neuronal activity on synaptic plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC) gating modifier, to manipulate [Na
+
]
i
in cerebrocortical neurons. The acute application of PbTx-2 produced concentration-dependent increments in both intracellular [Na
+
] and [Ca
2+
]. Pharmacological evaluation showed that PbTx-2–induced Ca
2+
influx primarily involved VGSC activation and NMDAR-mediated entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca
2+
influx. PbTx-2–exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor complexity, and increased dendritic filopodia density. The appearance of spontaneous calcium oscillations, reflecting synchronous neuronal activity, was accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth, dendritic arborization, and synaptogenesis all exhibited bidirectional concentration–response profiles. This profile paralleled that of NMDA, which also produced bidirectional concentration–response profiles for neurite outgrowth and synaptogenesis. These data are consistent with the hypothesis that PbTx-2–enhanced neuronal plasticity involves NMDAR-dependent signaling. Our results demonstrate that PbTx-2 mimics activity-dependent neuronal structural plasticity in cerebrocortical neurons through an increase in [Na
+
]
i
, up-regulation of NMDAR function, and engagement of downstream Ca
2+
-dependent signaling pathways. These data suggest that VGSC gating modifiers may represent a pharmacologic strategy to regulate neuronal plasticity through NMDAR-dependent mechanisms.
Human mitochondrial holocytochrome
c
synthase’s heme binding, maturation determinants, and complex formation with cytochrome
c
Authors: San Francisco Brian , Bretsnyder Eric C. , Kranz Robert G.
Published: November 2012

Proper functioning of the mitochondrion requires the orchestrated assembly of respiratory complexes with their cofactors. Cytochrome
c
, an essential electron carrier in mitochondria and a critical component of the apoptotic pathway, contains a heme cofactor covalently attached to the protein at a conserved CXXCH motif. Although it has been known for more than two decades that heme attachment requires the mitochondrial protein holocytochrome
c
synthase (HCCS), the mechanism remained unknown. We purified membrane-bound human HCCS with endogenous heme and in complex with its cognate human apocytochrome
c
. Spectroscopic analyses of HCCS alone and complexes of HCCS with site-directed variants of cytochrome
c
revealed the fundamental steps of heme attachment and maturation. A conserved histidine in HCCS (His154) provided the key ligand to the heme iron. Formation of the HCCS:heme complex served as the platform for interaction with apocytochrome
c
. Heme was the central molecule mediating contact between HCCS and apocytochrome
c
. A conserved histidine in apocytochrome
c
(His19 of CXXCH) supplied the second axial ligand to heme in the trapped HCCS:heme:cytochrome
c
complex. We also examined the substrate specificity of human HCCS and converted a bacterial cytochrome
c
into a robust substrate for the HCCS. The results allow us to describe the molecular mechanisms underlying the HCCS reaction.
Looking just below the eyes is optimal across face recognition tasks
Authors: Peterson Matthew F. , Eckstein Miguel P.
Published: November 2012

When viewing a human face, people often look toward the eyes. Maintaining good eye contact carries significant social value and allows for the extraction of information about gaze direction. When identifying faces, humans also look toward the eyes, but it is unclear whether this behavior is solely a byproduct of the socially important eye movement behavior or whether it has functional importance in basic perceptual tasks. Here, we propose that gaze behavior while determining a person’s identity, emotional state, or gender can be explained as an adaptive brain strategy to learn eye movement plans that optimize performance in these evolutionarily important perceptual tasks. We show that humans move their eyes to locations that maximize perceptual performance determining the identity, gender, and emotional state of a face. These optimal fixation points, which differ moderately across tasks, are predicted correctly by a Bayesian ideal observer that integrates information optimally across the face but is constrained by the decrease in resolution and sensitivity from the fovea toward the visual periphery (foveated ideal observer). Neither a model that disregards the foveated nature of the visual system and makes fixations on the local region with maximal information, nor a model that makes center-of-gravity fixations correctly predict human eye movements. Extension of the foveated ideal observer framework to a large database of real-world faces shows that the optimality of these strategies generalizes across the population. These results suggest that the human visual system optimizes face recognition performance through guidance of eye movements not only toward but, more precisely, just below the eyes.
Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs
Authors: Hu Yuanxin , Matkovich Scot J. , Hecker Peter A. , Zhang Yan , Edwards John R. , Dorn Gerald W.
Published: November 2012

Cardiac stress responses are driven by an evolutionarily conserved gene expression program comprising dozens of microRNAs and hundreds of mRNAs. Functionalities of different individual microRNAs are being studied, but the overall purpose of interactions between stress-regulated microRNAs and mRNAs and potentially distinct roles for microRNA-mediated epigenetic and conventional transcriptional genetic reprogramming of the stressed heart are unknown. Here we used deep sequencing to interrogate microRNA and mRNA regulation in pressure-overloaded mouse hearts, and performed a genome-wide examination of microRNA–mRNA interactions during early cardiac hypertrophy. Based on abundance and regulatory patterns, cardiac microRNAs were categorized as constitutively expressed housekeeping, regulated homeostatic, or dynamic early stress-responsive microRNAs. Regulation of 62 stress-responsive cardiac microRNAs directly affected levels of only 66 mRNAs, but the global impact of microRNA-mediated epigenetic regulation was amplified by preferential targeting of mRNAs encoding transcription factors, kinases, and phosphatases exerting amplified secondary effects. Thus, an emergent cooperative property of stress-regulated microRNAs is orchestration of transcriptional and posttranslational events that help determine the stress-reactive cardiac phenotype. This global functionality explains how large end-organ effects can be induced through modest individual changes in target mRNA and protein content by microRNAs that sense and respond dynamically to a changing physiological milieu.
Atypical angiopoietin-like protein that regulates ANGPTL3
Authors: Quagliarini Fabiana , Wang Yan , Kozlitina Julia , Grishin Nick V. , Hyde Rhonda , Boerwinkle Eric , Valenzuela David M. , Murphy Andrew J. , Cohen Jonathan C. , Hobbs Helen H.
Published: November 2012

Angiopoietin-like proteins (ANGPTLs) play major roles in the trafficking and metabolism of lipids. Inactivation of
ANGPTL3
, a gene located in an intron of
DOCK7
, results in very low levels of LDL-cholesterol (C), HDL-C and triglyceride (TAG). We identified another ANGPTL family member,
ANGPTL8
, which is located in the corresponding intron of
DOCK6
. A variant in this family member (rs2278426, R59W) was associated with lower plasma LDL-C and HDL-C levels in three populations. ANGPTL8 is expressed in liver and adipose tissue, and circulates in plasma of humans. Expression of ANGPTL8 was reduced by fasting and increased by refeeding in both mice and humans. To examine the functional relationship between the two ANGPTL family members, we expressed ANGPTL3 at physiological levels alone or together with ANGPTL8 in livers of mice. Plasma TAG level did not change in mice expressing ANGPTL3 alone, whereas coexpression with ANGPTL8 resulted in hypertriglyceridemia, despite a reduction in circulating ANGPTL3. ANGPTL8 coimmunoprecipitated with the N-terminal domain of ANGPTL3 in plasma of these mice. In cultured hepatocytes, ANGPTL8 expression increased the appearance of N-terminal ANGPTL3 in the medium, suggesting ANGPTL8 may activate ANGPTL3. Consistent with this scenario, expression of ANGPTL8 in
Angptl3

−/−

mice failed to promote hypertriglyceridemia. Thus,
ANGPTL8
, a paralog of
ANGPTL3
that arose through duplication of an ancestral
DOCK
gene, regulates postprandial TAG and fatty acid metabolism by controlling activation of its progenitor, and perhaps other ANGPTLs. Inhibition of ANGPTL8 provides a new therapeutic strategy for reducing plasma lipoprotein levels.
Reaction time and anticipatory skill of athletes in open and closed skill‐dominated sport
Authors: Nuri Leila , Shadmehr Azadeh , Ghotbi Nastaran , Attarbashi Moghadam Behrouz
Published: November 2012

In sports, reaction time and anticipatory skill are critical aspects of perceptual abilities. To date, no study has compared reaction time and anticipatory skill of athletes from open and closed skill‐dominated sport. Accordingly, the present study investigated whether a difference exists in sensory‐cognitive skills between these two different sport domains. Eleven volleyball players and 11 sprinters participated in this experiment. Reaction time and anticipatory skill of both groups were recorded by a custom‐made software called SART (speed anticipation and reaction time test). This software consists of six sensory‐cognitive tests that evaluate visual choice reaction time, visual complex choice reaction time, auditory choice reaction time, auditory complex choice reaction time, and anticipatory skill of the high speed and low speed of the ball. For each variable, an independent t‐test was performed. Results suggested that sprinters were better in both auditory reaction times (P<0.001 for both tests) and volleyball players were better in both anticipatory skill tests (P = 0.007 and P = 0.04 for anticipatory skill of the high speed and low speed of the ball, respectively). However, no significant differences were found in both visual choice reaction time tests (P > 0.05 for both visual reaction time tests). It is concluded that athletes have greater sensory‐cognitive skills related to their specific sport domain either open or closed.
Ilarviruses ofPrunusspp.: A Continued Concern for Fruit Trees
Authors: Pallas V. , Aparicio F. , Herranz M. C. , Amari K. , Sanchez-Pina M. A. , Myrta A. , Sanchez-Navarro J. A.
Published: November 2012

Prunus spp. are affected by a large number of viruses, causing significant economic losses through either direct or indirect damage, which results in reduced yield and fruit quality. Among these viruses, members of the genus Ilarvirus (isometric labile ringspot viruses) occupy a significant position due to their distribution worldwide. Although symptoms caused by these types of viruses were reported early in the last century, their molecular characterization was not achieved until the 1990s, much later than for other agronomically relevant viruses. This was mainly due to the characteristic liability of virus particles in tissue extracts. In addition, ilarviruses, together with Alfalfa mosaic virus, are unique among plant viruses in that they require a few molecules of the coat protein in the inoculum in order to be infectious, a phenomenon known as genome activation. Another factor that has made the study of this group of viruses difficult is that infectious clones have been obtained only for the type member of the genus, Tobacco streak virus. Four ilarviruses, Prunus necrotic ringspot virus, Prune dwarf virus, Apple mosaic virus, and American plum line pattern virus, are pathogens of the main cultivated fruit trees. As stated in the 9th Report of the International Committee on Taxonomy of Viruses, virions of this genus are “unpromising subjects for the raising of good antisera.” With the advent of molecular approaches for their detection and characterization, it has been possible to get a more precise view of their prevalence and genome organization. This review updates our knowledge on the incidence, genome organization and expression, genetic diversity, modes of transmission, and diagnosis, as well as control of this peculiar group of viruses affecting fruit trees.
THE SEASICK CHOROID
Authors: Arias Juan D. , Kumar Nishant , Fulco Enzo A. M. , Spaide Richard , Yannuzzi Lawrence , Shields Jerry A. , Shields Carol L.
Published: November 2012

Purpose:

To describe previously unreported imaging features of choroidal lymphoma using enhanced depth imaging optical coherence tomography (OCT).

Methods:

Enhanced depth imaging OCT was performed before and after the therapy.

Results:

A 32-year-old white man with a 4-month history of blurred vision in the right eye was found to have a macular fold. There was no visible intraocular tumor. There were no signs of anterior segment inflammation, vascular abnormalities, or infiltrative disease. Visual acuity was 20/150 in the right eye and 20/20 in the left eye. Enhanced depth imaging OCT demonstrated a macular retinal fold and marked thickening of the choroid with striking choroidal surface undulation and folds imparting an appearance similar to a “sea storm” (seasick appearance). Deep choroidal structures could not be visualized, and the sclerochoroidal interface could not be identified. Overlying subretinal fluid and intraretinal fluid was noted. Ultrasonography demonstrated diffuse, relatively smooth thickening of the choroid (4.0-mm thickness) with minor extraocular hypoechoic area. Based on these findings, choroidal lymphoid proliferation was suspected, and fine-needle aspiration biopsy confirmed B-cell lymphoma. Results of systemic evaluation were unremarkable. After external beam radiotherapy with dose of 40 Gy, visual acuity returned promptly to 20/40 and the lymphoid infiltration resolved with flattening of the macular fold and resolution of subretinal and intraretinal fluids. The enhanced depth imaging OCT returned to a more normal appearance with the resolution of the retinal fold and reduction of the choroidal mass with retinal pigment epithelial–choroidal surface features to a “calm sea” appearance.

Conclusion:

Enhanced depth imaging OCT is a useful tool for subclinical monitoring of choroidal infiltration from lymphoma before and after therapy.
TREATMENT OF CYSTOID MACULAR EDEMA IN A PATIENT WITH BIRDSHOT CHORIORETINOPATHY WITH BEVACIZUMAB
Authors: Hager Jon L. , Lewis Richard A. , Lambert H. Michael
Published: November 2012

Purpose:

Birdshot chorioretinopathy is currently treated with either systemic immune modulation or intravitreal polytherapy. These regimens pose challenges to the clinician and patient such as adverse effects, chronic treatment and compliance, and failure of therapy. In a patient with birdshot chorioretinopathy and juxtaposed cystoid macular edema, the authors assessed the efficacy of bevacizumab for treatment after systemic therapy had failed.

Methods:

A 48-year-old woman was injected with intravitreal bevacizumab 10 times in her right eye with 4 weeks to 6 weeks intervening between injections. Improvement was monitored by best-corrected visual acuity and ocular coherence tomography.

Results:

Visual acuity improved from 20/200 to 20/30 in the right eye, and foveal thickness improved from 638 μm to 200 μm. Visible signs of macular edema and inflammation completely disappeared.

Conclusion:

Bevacizumab monotherapy may improve visual acuity with resolution of macular edema in patients with birdshot chorioretinopathy that is refractory to traditional systemic therapy.
The evolution of photosystem I in light of phage-encoded reaction centres
Authors: Mazor Yuval , Greenberg Ilanit , Toporik Hila , Beja Oded , Nelson Nathan
Published: November 2012

Recent structural determinations and metagenomic studies shed light on the evolution of photosystem I (PSI) from the homodimeric reaction centre of primitive bacteria to plant PSI at the top of the evolutionary development. The evolutionary scenario of over 3.5 billion years reveals an increase in the complexity of PSI. This phenomenon of ever-increasing complexity is common to all evolutionary processes that in their advanced stages are highly dependent on fine-tuning of regulatory processes. On the other hand, the recently discovered virus-encoded PSI complexes contain a minimal number of subunits. This may reflect the unique selection scenarios associated with viral replication. It may be beneficial for future engineering of productive processes to utilize ‘primitive’ complexes that disregard the cellular regulatory processes and to avoid those regulatory constraints when our goal is to divert the process from its original route. In this article, we discuss the evolutionary forces that act on viral reaction centres and the role of the virus-carried photosynthetic genes in the evolution of photosynthesis.
Optimizing a flow-through X-ray transmission cell for studies of temporal and spatial variations of ion distributions at mineral–water interfaces
Authors: Lee Sang Soo , Fenter Paul , Park Changyong
Published: November 2012

The optimization of an X-ray transmission-cell design for high-resolution X-ray reflectivity measurements of the kinetics and thermodynamics of reactions at mineral–solution interfaces is presented. The transmission cell is equipped with a liquid flow system consisting of a pair of automated syringe pumps whose relative flow rates control the composition of a solution injected into the cell with ∼1% precision. The reflectivity measurements from the muscovite-(001)–solution interface at photon energies of 15–16.5 keV show that the cell is useful for probing interfacial ion adsorption–desorption experiments at a time scale of several seconds or slower. The time resolution is achieved with a small-volume (∼0.22 ml) reaction chamber to facilitate fast solution exchange. Additional reductions in reaction chamber volume will improve both the data quality by reducing X-ray absorption through the solution and the time resolution by increasing the solution exchange rate in the cell.
Eukaryotic versus prokaryotic marine picoplankton ecology
Authors: Massana Ramon , Logares Ramiro
Published: November 2012

Marine microorganisms contribute markedly to global biomass and ecosystem function. They include a diverse collection of organisms differing in cell size and in evolutionary history. In particular, microbes within the picoplankton are similar in size but belong to two drastically different cellular plans, the prokaryotes and the eukaryotes. Compared with larger organisms, prokaryotes and picoeukaryotes share ecological features, such as high specific activity, large and constant abundances, and high dispersal potential. Still, there are some aspects where their different cell organization influences their ecological performance. First, prokaryotes have a huge metabolic versatility and are involved in all biogeochemical cycles, whereas picoeukaryotes are metabolically less flexible but can exploit diverse predatory life strategies due to their phagocytic capacity. Second, sexual reproduction is absent in prokaryotes but may be present in picoeukaryotes, thus determining different evolutionary diversification dynamics and making species limits clearer in picoeukaryotes. Finally, it is plausible that picoeukaryotes are less flexible to enter a reversible state of low metabolic activity, thus picoeukaryote assemblages may have fewer rare species and may be less resilient to environmental change. In summary, lumping together pico‐sized microbes may be convenient for some ecological studies, but it is also important to keep in mind their differences.
Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?
Authors: Cardamone L , Salzberg MR , O'Brien TJ , Jones NC
Published: November 2012

There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer (‘second generation’) antidepressants, such as selective serotonin reuptake inhibitors or serotonin‐noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term ‘epileptogenesis’: the progressive neurobiological processes by which the non‐epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section.
TRPV1 and SP: key elements for sepsis outcome?
Authors: Bodkin Jennifer Victoria , Fernandes Elizabeth Soares
Published: November 2012

Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depends on the severity of systemic inflammation, which can be directly influenced by several factors, including the immune response of the patient. Currently, there is a lack of effective drugs to treat sepsis, and thus there is a need to develop new drugs to improve sepsis outcome. Several mediators involved in the formation of sepsis have now been identified, but the mechanisms underlying the pathology remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) receptor and the neuropeptide substance P (SP) have recently been demonstrated as important targets for sepsis and are located on sensory neurones and non‐neuronal cells. Herein, we highlight and review the importance of sensory neurones for the modulation of sepsis, with specific focus on recent findings relating to TRPV1 and SP, with their distinct abilities to alter the transition from local to systemic inflammation and also modify the overall sepsis outcome. We also emphasize the protective role of TRPV1 in this context.

Linked Articles

This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue‐7
Mine or Yours? Development of Sharing in Toddlers in Relation to Ownership Understanding
Authors: Brownell Celia A. , Iesue Stephanie S. , Nichols Sara R. , Svetlova Margarita
Published: November 2012

To examine early developments in other‐oriented resource sharing, fifty‐one 18‐ and 24‐month‐old children were administered 6 tasks with toys or food that could be shared with an adult playmate who had none. On each task the playmate communicated her desire for the items in a series of progressively more explicit cues. Twenty‐four‐month‐olds shared frequently and spontaneously. Eighteen‐month‐olds shared when given multiple opportunities and when the partner provided enough communicative support. Younger children engaged in self‐focused and hypothesis‐testing behavior in lieu of sharing more often than did older children. Ownership understanding, separately assessed, was positively associated with sharing and negatively associated with non‐sharing behavior, independent of age and language ability.
Ethnic differences in intraocular pressure reduction and changes in anterior segment biometric parameters following cataract surgery by phacoemulsification
Authors: Lee Roland Y , Kasuga Toshimitsu , Cui Qi N , Huang Guofu , Wang Sophia Y , Lin Shan C
Published: November 2012

Background

To determine the association between ethnicity and changes in intraocular pressure and anterior segment biometric parameters following cataract surgery by phacoemulsification in nonglaucomatous subjects.

Design

Prospective clinical cohort study.

Participants

Caucasian and Asian subjects.

Methods

Customized software was used to calculate parameters from anterior segment optical coherence tomography images obtained preoperatively and at 3 months following cataract surgery by phacoemulsification. The percentage changes in intraocular pressure and anterior segment biometric parameters following cataract surgery by phacoemulsification were modelled as a function of ethnicity using linear mixed‐effects regression, a likelihood ratio test function that adjusted for age, sex and the use of both eyes in the same subject, to determine the association between ethnicity and postoperative outcomes.

Main Outcome Measures

Intraocular pressure, angle opening distance, anterior chamber depth, anterior chamber volume, and angle recess area.

Results

Fifty Asian and 23 Caucasian nonglaucomatous eyes were analysed. Postoperative decrease in intraocular pressure and increases in angle opening distance, anterior chamber depth, anterior chamber volume and angle recess area were observed within each ethnic group (P < 0.005). The percent changes in intraocular pressure, angle opening distance, anterior chamber depth, anterior chamber volume and angle recess area did not differ between ethnic groups (P > 0.05).

Conclusions

In this study, regardless of ethnic classification, subjects who received cataract surgery by phacoemulsification experienced a significant postoperative decrease in intraocular pressure and increases in angle opening distance, anterior chamber depth, anterior chamber volume and angle recess area. The percent changes in postoperative outcomes did not differ significantly by ethnicity.
Aetiology and outcome of open and closed globe eye injuries in children
Authors: Kadappu Subhashini , Silveira Sue , Martin Frank
Published: November 2012

Background

This paper reports on the aetiology and outcome of childhood open and closed globe eye injuries presenting to the Children's Hospital at Westmead, Sydney, Australia from January 2000 to December 2008.

Design

Hospital‐based retrospective study.

Participants

Two hundred three cases of childhood eye injuries identified in a nine‐year period, comprising 81 open globe and 122 closed globe injuries.

Methods

Hospital records were examined for demographic data and injuries were classified into open globe and closed globe, based on the Ocular Trauma Classification.

Main Outcome Measures

Parameters affecting the final visual outcome such as type of injury, zone of injury, initial visual acuity, wound length (only in open globe injuries) and lens injury were assessed.

Results

Most of the eye injuries resulted from the child poking itself or being poked accidentally (26%), with the home being the most common place of injury. A favourable visual outcome was noted with closed globe injuries as compared with open globe injuries (P < 0.01). Parameters that indicated a poor visual outcome included globe ruptures, zone 3 injuries, poor initial visual acuity, wound length >10 mm and lens trauma. Final visual acuity of 6/12 or better was observed in 68% of injured eyes.

Conclusions

This study demonstrated improved visual outcomes when compared with previous studies. However, many unsalvageable childhood eye injuries with little useful vision were evident, and most disconcerting is that the majority of childhood eye injuries in this study were preventable.
Pharmacokinetics and safety of adjunctive topiramate in infants (1–24 months) with refractory partial‐onset seizures: A randomized, multicenter, open‐label phase 1 study
Authors: Manitpisitkul Prasarn , Shalayda Kevin , Todd Mike , Wang Shean S. , Ness Seth , Ford Lisa
Published: November 2012

Purpose:  To characterize the pharmacokinetics of adjunctive topiramate in infants (1–24 months) with refractory partial‐onset seizures (POS); also to evaluate safety and tolerability of topiramate in the dose range of 3–25 mg/kg/day.

Methods:  In this open‐label phase 1 study, infants (N = 55) with refractory POS receiving at least one concurrent antiepileptic drug (AED) were enrolled. Infants were stratified by age and randomly assigned to one of four topiramate target dose groups (3‐, 5‐, 15‐, or 25 mg/kg/day). Treatment was initiated at 3 mg/kg/day with titration to the target dose by weekly dose escalation. Topiramate was administered daily in two divided doses as oral liquid (5 mg/ml for infants <9 kg or those who could not tolerate solid foods) or sprinkle capsule (25 mg) formulations. Following seven consecutive days of topiramate administration at the target dose, four blood samples were collected from each infant for pharmacokinetic assessments (predose, 1–3, 4–6, and 8–10 h postdose).

Key Findings:  Fifty‐five infants (mean [SD] age in months: 11.4 [5.79]) with POS were enrolled, of whom 33% had seizures with or without secondary generalization. Complete pharmacokinetic profiles were obtained in 35 infants in whom mean plasma topiramate concentration–time profiles demonstrated linear pharmacokinetics (predose topiramate concentrations [Ctrough] and area under the plasma concentration–time curve from time 0 through 12 h [AUC12 h]) of topiramate over the dose range studied). Apparent steady state oral clearance (CLss/F) remained similar across all topiramate target dose groups and was independent of creatinine clearance, age, and weight. Mean values for CLss/F were approximately twofold greater in infants receiving concomitant enzyme‐inducing AEDs versus enzyme‐inhibiting AEDs. Topiramate was well tolerated and safety findings were consistent with previous reports in children and adults. Most common treatment emergent adverse events (≥10%) were upper respiratory tract infection, fever, vomiting, somnolence, and anorexia.

Significance:  In infants (1–24 months), topiramate exhibited linear steady state pharmacokinetics over the dose range 3–25 mg/kg/day, and CLss/F of topiramate was independent of dose. Moreover, the concomitant enzyme‐inducing AEDs doubled the clearance of topiramate. Topiramate was generally well tolerated as adjunctive therapy at doses up to 25 mg/kg/day.
Inborn errors of creatine metabolism and epilepsy
Authors: Leuzzi Vincenzo , Mastrangelo Mario , Battini Roberta , Cioni Giovanni
Published: November 2012

Creatine metabolism disorders include guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CT1‐encoded by SLC6A8 gene) deficiency. Epilepsy is one of the main symptoms in GAMT and CT1 deficiency, whereas the occurrence of febrile convulsions in infancy is a relatively common presenting symptom in all the three above‐mentioned diseases. GAMT deficiency results in a severe early onset epileptic encephalopathy with development arrest, neurologic deterioration, drug‐resistant seizures, movement disorders, mental disability, and autistic‐like behavior. In this disorder, epilepsy and associated abnormalities on electroencephalography (EEG) are more responsive to substitutive treatment with creatine monohydrate than to conventional antiepileptic drugs. AGAT deficiency is mainly characterized by mental retardation and severe language disorder without epilepsy. In CT1 deficiency epilepsy is generally less severe than in GAMT deficiency. All creatine disorders can be investigated through measurement of creatine metabolites in body fluids, brain proton magnetic resonance spectroscopy (1H‐MRS), and molecular genetic techniques. Blood guanidinoacetic acid (GAA) assessment and brain H‐MRS examination should be part of diagnostic workup for all patients presenting with epileptic encephalopathy of unknown origin. In girls with learning and/or intellectual disabilities with or without epilepsy, SLC6A8 gene assessment should be part of the diagnostic procedures. The aims of this review are the following: (1) to describe the electroclinical features of epilepsy occurring in inborn errors of creatine metabolism; and (2) to delineate the metabolic alterations associated with GAMT, AGAT, and CT1 deficiency and the role of a substitutive therapeutic approach on their clinical and electroencephalographic epileptic patterns.
Brain gene expression differences are associated with abnormal tail biting behavior in pigs
Authors: Brunberg E. , Jensen P. , Isaksson A. , Keeling L. J.
Published: November 2012

Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior.
The carbon count of 2000 years of rice cultivation
Authors: Kalbitz Karsten , Kaiser Klaus , Fiedler Sabine , Kölbl Angelika , Amelung Wulf , Bräuer Tino , Cao Zhihong , Don Axel , Grootes Piet , Jahn Reinhold , Schwark Lorenz , Vogelsang Vanessa , Wissing Livia , Kögel‐Knabner Ingrid
Published: November 2012

More than 50% of the world's population feeds on rice. Soils used for rice production are mostly managed under submerged conditions (paddy soils). This management, which favors carbon sequestration, potentially decouples surface from subsurface carbon cycling. The objective of this study was to elucidate the long‐term rates of carbon accrual in surface and subsurface soil horizons relative to those of soils under nonpaddy management. We assessed changes in total soil organic as well as of inorganic carbon stocks along a 2000‐year chronosequence of soils under paddy and adjacent nonpaddy management in the Yangtze delta, China. The initial organic carbon accumulation phase lasts much longer and is more intensive than previously assumed, e.g., by the Intergovernmental Panel on Climate Change (IPCC). Paddy topsoils accumulated 170–178 kg organic carbon ha−1 a−1 in the first 300 years; subsoils lost 29–84 kg organic carbon ha−1 a−1 during this period of time. Subsoil carbon losses were largest during the first 50 years after land embankment and again large beyond 700 years of cultivation, due to inorganic carbonate weathering and the lack of organic carbon replenishment. Carbon losses in subsoils may therefore offset soil carbon gains or losses in the surface soils. We strongly recommend including subsoils into global carbon accounting schemes, particularly for paddy fields.
Physical and Mechanical Properties of Barium Alkali Silicate Glasses for SOFC Sealing Applications
Authors: Trejo Rosa , Lara‐Curzio Edgar , Shyam Amit , Kirkham Melanie J. , Garcia‐Negron Valerie , Wang Yanli
Published: November 2012

The physical and mechanical properties of two barium alkali silicate glasses were determined as a function of temperature. Their Young's modulus and Poisson's ratio were determined by resonant ultrasound spectroscopy; their viscosity, thermal expansion, and glass transition temperature were determined using a thermomechanical analyzer. The wetting behavior of the two glasses on alumina and 8 mol% yttria stabilized zirconia (8YSZ) substrates was determined by measuring contact angles in air as a function of temperature and time. Values of Young's modulus for both glasses were in good agreement with those predicted by the Makishima and MacKenzie model. The physical and mechanical properties of these glasses are discussed in the context of their potential use for sealing applications in solid‐oxide fuel cells.
Legitimizing Diverse Uses for Qualitative Research: A Rhetorical Analysis of Two Management Journals
Authors: Welch Catherine , Plakoyiannaki Emmanuella , Piekkari Rebecca , Paavilainen‐Mäntymäki Eriikka
Published: November 2012

This paper examines how management researchers rhetorically construct the theoretical purpose and contribution of qualitative studies. By means of a rhetorical analysis of qualitative studies published in theAcademy ofManagementJournalandJournal ofManagementStudies, we identify three sets of rhetorical practices, or repertoires, in the period 1999–2011. These repertoires differ with regard to how they position and legitimize the use of qualitative research. The first repertoire, which we label ‘modernist’, bases the legitimacy of qualitative research on its exploratory and theory‐building strengths. The second ‘revisionist’ repertoire accepts key assumptions of modernism, but allows for an expanded role for qualitative research. In contrast, the third ‘subversive’ repertoire is non‐positivist and rejects the traditional theory‐building/‐testing dichotomy. Using the insights from our ‘rhetoric of science’ approach, we argue for the use of alternative repertoires that decouple qualitative research from the rhetoric of exploration.