bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep disorders
Authors: Reading Paul
Published: January 2012

Despite major advances in our understanding of its neurobiology, sleep remains an enigma. Its true function and even the amount needed for optimum brain performance remain uncertain (Frank 2006). However, the need to sleep is imperative, reflecting the fact that sleepiness, like hunger and thirst, is a true drive state. Sleepiness can only be satiated by sleep itself. Moreover, severely disordered sleep can profoundly affect cognition, mental health, and physical well-being.

Although sleep medicine has a traditionally low profile in neurology teaching and practice, sleep-related phenomena are frequently associated with numerous neurological disorders. Conversely, sleep problems can adversely affect familiar conditions such as headache and epilepsy. Furthermore, in large surveys, sleep-related symptoms are undoubtedly common with 25 per cent of the population reporting problems that significantly and regularly impact on daily activities.
Neuropsychological disorders, dementia, and behavioural neurology
Authors: Rossor Martin
Published: January 2012

The diseases which disrupt the cerebral cortex and its subcortical connections result in a wide variety of clinical features. These include the classical syndromes of higher cortical dysfunction such as the dysphasias, dyspraxias, amnesias, and agnosias together with a wide variety of behavioural and emotional disturbances. Such disorders frequently overlap with the clinical disciplines of clinical psychology and psychiatry. Historically there has been a broad split between those diseases which are seen by neurologists and those that are seen by psychiatrists. To some extent the distinction reflects the different clinical approaches employed; neurologists concentrate on the generality of disease caused by lesions in defined areas, whereas psychiatrists often deal with diseases that show a greater interaction with the individuals own personal history and place in society (Lishman 1987). In this chapter disturbances of higher cortical function, the dementias, and behavioural aspects of neurological lesions are discussed. Awareness of the occasional presentation of psychiatric disease to the neurologists is important and further details are available in textbooks of psychiatry. A review of clinical syndromes referable to identified areas of the cerebral cortex, is followed by a functional approach which discusses the main neuropsychological syndromes. The more generalized cognitive impairment seen with the dementias such as Alzheimer’s disease, dementia with Lewy bodies, and the frontotemporal lobar degenerations are then reviewed followed by areas of neuropsychiatric overlap.
Vasculitis and collagen vascular diseases
Authors: Scolding Neil
Published: January 2012

That part of the clinical interface between neurology and general medicine occupied by inflammatory and immunological diseases is neither small nor medically trivial. Neurologists readily accept the challenges of ‘primary’ immune diseases of the nervous system: these tend to be focussed on one particular target such as oligodendrocytes or the neuro-muscular junction present in predictable ways, and are amenable as a rule to rational, methodological diagnosis, and occasionally even treatment. This is proper neurology.

‘Secondary’ neurological involvement in diseases mainly considered systemic inflammatory conditions—for example, SLE, sarcoidosis, vasculitis, and Behçet’s—is a rather different matter. It may be difficult enough to secure such a diagnosis even when systemic disease has previously been diagnosed and new neurological features need to be differentiated from iatrogenic disease, particularly drug side effects or the consequences of immune suppression. But all the diseases mentioned may present with and confine themselves wholly to the nervous system; they may mimic one another, and pursue erratic and unpredictable clinical courses. In central nervous system disease, diagnosis by tissue biopsy is potentially hazardous and unattractive. Few neurologists enjoy excesses of confidence or expertise when faced with such clinical problems: the cautious diagnostician is perplexed, and the evidence-based neuroprescriber confounded. Unsurprisingly, great variations in approaches to diagnosis and management are seen (Scolding et al. 2002b).

But rheumatologically inclined general, renal or respiratory physicians, comfortable when managing inflammation affecting their system or indeed other parts of the body designed to support the nervous system, are generally also ill at ease when faced with neurological features whose differential diagnosis may be large, particularly given the near universal diagnostic non-specificity of either imaging or CSF analysis.

Here then is the subject material for this chapter: the diagnosis and management of central nervous system involvement in inflammatory and immunological systemic diseases (Scolding 1999a). In not one of these neurological conditions has a single controlled therapeutic trial been reported, and much that is published on these conditions is misleading or inaccurate. And yet the frequency with which the diagnosis is only confirmed or even first emerges at autopsy bears stark witness to both the severity and evasiveness of these disorders.
Paraneoplastic disorders and neuroimmunology
Authors: Scolding Neil
Published: January 2012

The extraordinary expansion in the field of neuroimmunology witnessed in the last decade is not just in the number of neurological disorders now considered to have an immune basis, nor the depth of understanding of disorders long known to be ‘neuroimmune’. Nor is it in the number of antibodies discovered and now testable, nor in the range of new immune suppressant or modifying treatments now emerging or already available. It is of course all of these things, but it is also more than the sum of these parts. What we are currently privileged to witness is the coming together of immunological understanding, the neurobiology of disease, and rational immune therapy, or at least the beginning of this process. To take one isolated example, neurogenetics and neurophysiology taught us about the clinical consequences of channel disruption; laboratory-based neuroimmunology showed antibodies to be capable of producing comparable acquired disease; and it seems likely that specific anti-B-cell humanized monoclonal antibodies offer the therapeutic potential to remove these channel-disrupting antibodies. Neither of these steps could be described in the last edition, and one can imagine similar dramatic changes will emerge before the next.
Tremor, ataxia, and cerebellar disorders
Authors: Fletcher Nicholas
Published: January 2012

Tremors are characterized by rhythmic oscillations of one or more body parts. Although typically seen in the upper limbs, almost any area may be involved, including the trunk, head, facial muscles, and legs. Sometimes, tremor is not visible at all but may be heard or palpated, for example, in vocal or orthostatic tremor, respectively. In neurological practice, the diagnosis and treatment of tremor is an everyday problem. A common scenario is the distinction between essential tremor and Parkinson’s disease. In this chapter, the wide range of tremors are discussed, with their aetiolology, pathophysiology, diagnosis and management described.

Ataxia is a term used to describe a wide range of neurological disorders affecting muscle coordination, speech and balance that reflect dysfunction of a part of the central nervous system involved in motor function. Many of ataxias have a cerebellar pathology as root cause, although it must be remembered that ataxia, clumsiness, disordered ocular motility, dysarthria, and even kinetic or intention tremor are not always caused by cerebellar disease. This chapter describes the wide range of cerebellar disorders and ataxias, as are non-cerebellar ataxias such as Friedreich’s ataxia.
Meningitis
Authors: Solomon Tom
Published: January 2012

Meningitis is defined as inflammation of the brain meninges, characterized clinically by inflammatory cells in CSF. When there is concurrent parenchymal brain involvement the term meningoencephalitis is used, meningoencephalomyelitis implies that there is spinal cord involvement too.

Although increased cellularity in the CSF, or pleocytosis, is traditionally considered the hallmark of meningitis, some organisms, particularly fungi, can cause meningitis without a pleocytosis, especially in the immunocompromised. The advent of more sensitive methods of detecting viral nucleic acid in the CSF such as the polymerase chain reaction, have also shown that viral central nervous system infection can occur without an associated pleocytosis. When none of the common bacterial agents is easily identified the term aseptic meningitis is often used. The majority of such cases are caused by viruses; non-viral causes of an aseptic meningitis picture include certain bacteria which are not readily cultured, and do not grow in standard culture media, such as Borrelia burgdorferi. The clinical presentations of meningitis can be broadly divided into the acute, recurrent, and chronic. The development of meningitis depends on the infecting organism, and also whether there is any particular host susceptibility.
Intracranial space occupying infections and neurological HIV disease
Authors: Solomon Tom
Published: January 2012

This chapter begins with a discussion of space occupying lesions. It ends with a review of the neurological complications of HIV, which encompasses patients presenting with all central nervous system syndromes, including meningitis, reduced consciousness, myelopathy, and space occupying lesions.
Broad-Spectrum Acquired Resistance in Barley Induced by thePseudomonasPathosystem Shares Transcriptional Components withArabidopsisSystemic Acquired Resistance
Authors: Colebrook E. H. , Creissen G. , McGrann G. R. D. , Dreos R. , Lamb C. , Boyd L. A.
Published: January 2012

Inducible resistance responses play a central role in the defense of plants against pathogen attack. Acquired resistance (AR) is induced alongside defense toward primary attack, providing broad-spectrum protection against subsequent pathogen challenge. The localization and molecular basis of AR in cereals is poorly understood, in contrast with the well-characterized systemic acquired resistance (SAR) response in Arabidopsis. Here, we use Pseudomonas syringae as a biological inducer of AR in barley, providing a clear frame of reference to the Arabidopsis–P. syringae pathosystem. Inoculation of barley leaf tissue with the nonadapted P. syringae pv. tomato avrRpm1 (PstavrRpm1) induced an active local defense response. Furthermore, inoculation of barley with PstavrRpm1 resulted in the induction of broad-spectrum AR at a distance from the local lesion, “adjacent” AR, effective against compatible isolates of P. syringae and Magnaporthe oryzae. Global transcriptional profiling of this adjacent AR revealed similarities with the transcriptional profile of SAR in Arabidopsis, as well as transcripts previously associated with chemically induced AR in cereals, suggesting that AR in barley and SAR in Arabidopsis may be mediated by analogous pathways.
Sugarwin: A Sugarcane Insect-Induced Gene with Antipathogenic Activity
Authors: Medeiros Ane H. , Franco Flávia P. , Matos Juliana L. , de Castro Patrícia A. , Santos-Silva Ludier K. , Henrique-Silva Flávio , Goldman Gustavo H. , Moura Daniel S. , Silva-Filho Marcio C.
Published: January 2012

In sugarcane fields, colonization of the stalk by opportunistic fungi usually occurs after the caterpillar Diatraea saccharalis attacks the sugarcane plant. Plants respond to insect attack by inducing and accumulating a large set of defense proteins. Two homologues of a barley wound-inducible protein (BARWIN), sugarcane wound-inducible proteins SUGARWIN1 and SUGARWIN2, have been identified in sugarcane by an in silico analysis. Antifungal properties have been described for a number of BARWIN homologues. We report that a SUGARWIN::green fluorescent protein fusion protein is located in the endoplasmic reticulum and in the extracellular space of sugarcane plants. The induction of sugarwin transcripts occurs in response to mechanical wounding, D. saccharalis damage, and methyl jasmonate treatment. The accumulation of transcripts is late induced and is restricted to the site of the wound. Although the transcripts of sugarwin genes were strongly increased following insect attack, the protein itself did not show any effect on insect development; rather, it altered fungal morphology, leading to the apoptosis of the germlings. These results suggest that, in the course of evolution, sugarwin-encoding genes were recruited by sugarcane due to their antipathogenic activity. We rationalize that sugarcane is able to induce sugarwin gene expression in response to D. saccharalis feeding as a concerted plant response to the anticipated invasion by the fungi that typically penetrate the plant stalk after insect damage.
Quantitative Variation in Effector Activity of ToxA Isoforms fromStagonospora nodorumandPyrenophora tritici-repentis
Authors: Tan Kar-Chun , Ferguson-Hunt Margo , Rybak Kasia , Waters Ormonde D. C. , Stanley Will A. , Bond Charles S. , Stukenbrock Eva H. , Friesen Timothy L. , Faris Justin D. , McDonald Bruce A. , Oliver Richard P.
Published: January 2012

ToxA is a proteinaceous necrotrophic effector produced by Stagonospora nodorum and Pyrenophora tritici-repentis. In this study, all eight mature isoforms of the ToxA protein were purified and compared. Circular dichroism spectra indicated that all isoforms were structurally intact and had indistinguishable secondary structural features. ToxA isoforms were infiltrated into wheat lines that carry the sensitivity gene Tsn1. It was observed that different wheat lines carrying identical Tsn1 alleles varied in sensitivity to ToxA. All ToxA isoforms induced necrosis when introduced into any Tsn1 wheat line but we observed quantitative variation in effector activity, with the least-active version found in isolates of P. tritici-repentis. Pathogen sporulation increased with higher doses of ToxA. The isoforms that induced the most rapid necrosis also induced the most sporulation, indicating that pathogen fitness is affected by differences in ToxA activity. We show that differences in toxin activity encoded by a single gene can contribute to the quantitative inheritance of necrotrophic virulence. Our findings support the hypothesis that the variation at ToxA results from selection that favors increased toxin activity.
Water bathing alters threat perception in starlings
Authors: Brilot Ben O. , Bateson Melissa
Published: January 2012

The majority of bird taxa perform water bathing, but little is known about the adaptive value of this behaviour. If bathing is important for feather maintenance then birds that have not bathed should have poorer feather condition, compromised escape ability and therefore increased responsiveness to cues of predation. We conducted two experiments examining the behaviour of captive starlings responding to conspecific alarm calls. Birds that had no access to bathing water showed a decreased willingness to feed and increased their vigilance behaviour following an alarm call. We argue that birds denied access to bathing water interpreted an ambiguous cue of threat as requiring more caution than birds that had access, consistent with higher levels of anxiety. Our results support the provision of bathing water for captive birds as an important welfare measure.
Large Hadron Collider commissioning and first operation
Authors: Myers S.
Published: January 2012

A history of the commissioning and the very successful early operation of the Large Hadron Collider (LHC) is described. The accident that interrupted the first commissioning, its repair and the enhanced protection system put in place are fully described. The LHC beam commissioning and operational performance are reviewed for the period from 2010 to mid-2011. Preliminary plans for operation and future upgrades for the LHC are given for the short and medium term.
Outstanding questions: physics beyond the Standard Model
Authors: Ellis John
Published: January 2012

The Standard Model of particle physics agrees very well with experiment, but many important questions remain unanswered, among them are the following. What is the origin of particle masses and are they due to a Higgs boson? How does one understand the number of species of matter particles and how do they mix? What is the origin of the difference between matter and antimatter, and is it related to the origin of the matter in the Universe? What is the nature of the astrophysical dark matter? How does one unify the fundamental interactions? How does one quantize gravity? In this article, I introduce these questions and discuss how they may be addressed by experiments at the Large Hadron Collider, with particular attention to the search for the Higgs boson and supersymmetry.
Physics requirements for the design of the ATLAS and CMS experiments at the Large Hadron Collider
Authors: Virdee T. S.
Published: January 2012

The ATLAS and CMS experiments at the CERN Large Hadron Collider are discovery experiments. Thus, the aim was to make them sensitive to the widest possible range of new physics. New physics is likely to reveal itself in addressing questions such as: how do particles acquire mass; what is the particle responsible for dark matter; what is the path towards unification; do we live in a world with more space–time dimensions than the familiar four? The detection of the Higgs boson, conjectured to give mass to particles, was chosen as a benchmark to test the performance of the proposed experiment designs. Higgs production is one of the most demanding hypothesized processes in terms of required detector resolution and background discrimination. ATLAS and CMS feature full coverage, 4
π
-detectors to measure precisely the energies, directions and identity of all the particles produced in proton–proton collisions. Realizing this goal has required the collaborative efforts of enormous teams of people from around the world.
The Large Hadron Collider project: organizational and financial matters (of physics at the terascale)
Authors: Engelen Jos
Published: January 2012

In this paper, I present a view of organizational and financial matters relevant for the successful construction and operation of the experimental set-ups at the Large Hadron Collider of CERN, the European Laboratory for Particle Physics in Geneva. Construction of these experiments was particularly challenging: new detector technologies had to be developed; experimental set-ups that are larger and more complex than ever before had to be constructed; and larger collaborations than ever before had to be organized. Fundamental to the success were: the ‘reference’ provided by CERN, peer review, signed memoranda of understanding, well-organized resources review boards as an interface to the national funding agencies and collegial, but solidly organized, experimental collaborations.
The future of the Large Hadron Collider and CERN
Authors: Heuer Rolf-Dieter
Published: January 2012

This paper presents the Large Hadron Collider (LHC) and its current scientific programme and outlines options for high-energy colliders at the energy frontier for the years to come. The immediate plans include the exploitation of the LHC at its design luminosity and energy, as well as upgrades to the LHC and its injectors. This may be followed by a linear electron–positron collider, based on the technology being developed by the Compact Linear Collider and the International Linear Collider collaborations, or by a high-energy electron–proton machine. This contribution describes the past, present and future directions, all of which have a unique value to add to experimental particle physics, and concludes by outlining key messages for the way forward.
Heavy-ion physics with the ALICE experiment at the CERN Large Hadron Collider
Authors: Schukraft J.
Published: January 2012

After close to 20 years of preparation, the dedicated heavy-ion experiment A Large Ion Collider Experiment (ALICE) took first data at the CERN Large Hadron Collider (LHC) accelerator with proton collisions at the end of 2009 and with lead nuclei at the end of 2010. After a short introduction into the physics of ultra-relativistic heavy-ion collisions, this article recalls the main design choices made for the detector and summarizes the initial operation and performance of ALICE. Physics results from this first year of operation concentrate on characterizing the global properties of typical, average collisions, both in proton–proton (pp) and nucleus–nucleus reactions, in the new energy regime of the LHC. The pp results differ, to a varying degree, from most quantum chromodynamics-inspired phenomenological models and provide the input needed to fine tune their parameters. First results from Pb–Pb are broadly consistent with expectations based on lower energy data, indicating that high-density matter created at the LHC, while much hotter and larger, still behaves like a very strongly interacting, almost perfect liquid.
4-Carboxypiperidinium 1-carboxycyclobutane-1-carboxylate
Authors: Belandria Lusbely M. , Mora Asiloé J. , Delgado Gerzon E. , Briceño Alexander
Published: January 2012

The title salt, C6H12NO2+·C6H7O4−or ISO+·CBDC−, is an ionic ensemble assisted by hydrogen bonds. The amino acid moiety (ISO or piperidine-4-carboxylic acid) has a protonated ring N atom (ISO+or 4-carboxypiperidinium), while the semi-protonated acid (CBDC−or 1-carboxycyclobutane-1-carboxylate) has the negative charge residing on one carboxylate group, leaving the other as a neutral –COOH group. The –+NH2– state of protonation allows the formation of a two-dimensional crystal packing consisting of zigzag layers stacked alongaseparated by van der Waals distances. The layers extend in thebcplane connected by a complex network of N—H...O and O—H...O hydrogen bonds. Wave-like ribbons, constructed from ISO+and CBDC−units and described by the graph-set symbolsC33(10) andR33(14), run alternately in opposite directions alongc. Intercalated between the ribbons are ISO+cations linked by hydrogen bonds, forming rings described by the graph-set symbolsR66(30) andR42(18). A detailed analysis of the structures of the individual components and the intricate hydrogen-bond network of the crystal structure is given.
Study of the single-crystal X-ray diffuse scattering in paracetamol polymorphs
Authors: Chan E. J. , Goossens D. J.
Published: January 2012

Single-crystal diffuse X-ray scattering from paracetamol polymorphs is successfully calculated with Monte Carlo (MC) models that are used to simulate the crystals. In order to obtain the correct model appropriate force constants are required that describe the interatomic potentials used in the MC algorithm. Coefficients for an empirical `Buckingham'-type formula are used to determine these force constants. These coefficients are subsequently refined using the least-squares method and are found to converge on similar values for both polymorphic forms. An investigation of the correlation space generated from each model provides what would be expected given that strong displacive correlations exist between the molecules comprising the densely hydrogen-bonded layers. More disordered motions between these layers are present in the model for form (II) as opposed to form (I). An investigation into the peculiarities of librational disorder was also conducted, however, correlation values turn out to be so small that any structural information concerning librational correlation is inconclusive. The purpose of this experiment was to identify if the diffuse scattering features could provide further insight into understanding the physical reasoning behind the metastability of form (II). The form (II) → (I) phase transition is also not currently well understood and usually phase transitional information can be obtained from pronounced diffuse scattering features. Since the diffuse scattering is modelled adequately using harmonic potentials it is our conjecture that the `diffuse' is essentially thermal in origin and does not afford any extra information about the form (II) → (I) phase transition.
Structure maps for A
I
4
A
II
6(BO4)6X2 apatite compounds via data mining
Authors: Balachandran Prasanna V. , Rajan Krishna
Published: January 2012

This paper describes a method to identify key crystallographic parameters that can serve as strong classifiers of crystal chemistries and hence define new structure maps. The selection of this pair of key parameters from a large set of potential classifiers is accomplished through a linear data-dimensionality reduction method. A multivariate data set of known A
I
4
A
II
6(BO4)6
X
2 apatites is used as the basis for the study where each A
I
4
A
II
6(BO4)6
X
2 compound is represented as a 29-dimensional vector, where the vector components are discrete scalar descriptors of electronic and crystal structure attributes. A new structure map, defined using the two distortion angles αAII (rotation angle of A
II—A
II—A
II triangular units) and ψAIz = 0
AI—O1 (angle the A
I—O1 bond makes with the c axis when z = 0 for the A
I site), is shown to classify apatite crystal chemistries based on site occupancy on the A, B and X sites. The classification is accomplished using a K-means clustering analysis.
Revision of the Mg(ClO4)2·4H2O crystal structure
Authors: Solovyov Leonid A.
Published: January 2012

A revision is presented of the restrained Rietveld analysis of the crystal structure of magnesium perchlorate tetrahydrate, Mg(ClO4)2·4H2O, recently published by Robertson & Bish [(2010), Acta Cryst. B66, 579–584]. The actual symmetry of the material is shown to be C2/m. The corrected structure model is refined by the derivative difference method [Solovyov (2004). J. Appl. Cryst.
37, 743–749], anisotropically for all non-H atoms and isotropically for two independent H atoms without restraints.
Spinal anaesthesia for caesarean delivery in a parturient with babesiosis and Lyme disease
Authors: Sultan P. , Green C. , Riley E. , Carvalho B.
Published: January 2012

We present a case of a parturient with babesiosis and Lyme disease who was scheduled for elective caesarean section. The caesarean section was performed under spinal anaesthesia, and the patient had a coronary artery dissection 4 days postoperatively. Neuraxial anaesthesia and possible mechanisms for the coronary artery dissection in a patient with babesiosis and Lyme disease are discussed.
H1‐antihistamines and urticaria: how can we predict the best drug for our patient?
Authors: Church M. K. , Maurer M.
Published: January 2012

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H1‐antihistamines currently available and the pharmaceutical industries need to keep developing H1‐antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head‐to‐head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H1‐antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H1‐antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine‐induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.
The investigation of severe asthma to define phenotypes
Authors: Gibeon D. , Chung K. F.
Published: January 2012

Severe asthmatics often exhibit poor control despite high doses of inhaled corticosteroids with or without systemic corticosteroids and suffer from persistent symptoms and/or recurrent exacerbations. Five to ten percentage of the asthmatic population falls within this category. Patients with severe asthma are a heterogeneous group and should be investigated to confirm the diagnosis, identify comorbidities, exclude alternative diagnoses, together with an evaluation of treatment adherence and side‐effects from medications. Optimization of asthma medications and monitoring the control and pattern of asthma usually takes place over a period of 6 months. In patients with confirmed severe refractory asthma, further evaluation is needed in terms of detailed lung function, of airway and lung structure using high resolution computed tomographic scanning, and of airway inflammatory processes and biomarkers using induced sputum or bronchial biopsies. Patients with severe asthma are best investigated and managed with a multidisciplinary team. Severe asthma consists of different phenotypes that need defining. Investigation of severe asthma should bring into the open the various characteristics of the disease that could point to particular phenotype. Inclusion of investigations based on transcriptomics and proteomics should expand, improve classification and understanding of severe asthma, with the ultimate hope of finding more effective treatments and a step towards personalized medicine.
Molecular characterization of wheat allergens specifically recognized by patients suffering from wheat‐induced respiratory allergy
Authors: Pahr S. , Constantin C. , Mari A. , Scheiblhofer S. , Thalhamer J. , Ebner C. , Vrtala S. , Mittermann I. , Valenta R.
Published: January 2012

Background

Wheat (Triticum aestivum) is an important allergen source responsible for various clinical manifestations of allergy (i.e. food allergy, pollen allergy, respiratory allergy to flour‐Baker's asthma).

Objective

The objective of this study was the molecular and immunological characterization of new recombinant wheat allergens and to evaluate their usefulness for the diagnosis of allergy to wheat.

Methods

A T. aestivum cDNA library was constructed and screened with serum IgE from patients suffering from wheat allergy to identify cDNAs coding for new wheat allergens. The allergen‐encoding cDNAs were expressed in Escherichia coli and purified to homogeneity. IgE reactivity of recombinant proteins was analysed in RAST‐based, non‐denaturing dot blot experiments and by ELISA with sera from wheat allergic patients and their allergenic activity was assessed in basophil degranulation experiments.

Results

We report the molecular characterization, recombinant expression and purification of five wheat allergens, a thioredoxin h isoform, glutathione transferase, 1‐Cys‐peroxiredoxin, profilin and dehydrin. Homologous proteins were identified by sequence comparisons in various plants. 1‐Cys‐peroxiredoxin appeared to be the most relevant of the newly identified wheat allergens according to prevalence of IgE recognition and results from basophil degranulation experiments. It showed IgE cross‐reactivity with seed proteins from barley, rye, rice, maize, soy, oat and spelt. 1‐Cys‐peroxiredoxin, glutathione transferase and dehydrin were mainly recognized by patients with baker's asthma but not wheat‐induced food allergy.

Conclusion and Clinical Relevance

The characterized recombinant wheat allergens may be useful for the development of serological tests which allow the discrimination of different clinical manifestations of wheat allergy.
Identification of serotype-specific T cell responses to highly conserved regions of the dengue viruses
Authors: Malavige G N , McGowan S , Atukorale V , Salimi M , Peelawatta M , Fernando N , Jayaratne S D , Ogg G
Published: January 2012

Determining previous infecting dengue virus (DENV) serotypes has been difficult due to highly cross-reactive immune responses from previous DENV infections. Determining the correlates of serotype-specific immune responses would be crucial in understanding dengue transmission in the community and would also help to determine the correlates of protective immune responses. Therefore, we set out to define highly conserved, serotype-specific regions of the DENVs. Serotype-specific and highly conserved regions of the four DENV serotypes were identified using Basic Local Alignment Search Tool (BLAST) searches and custom perl scripts. Using ex-vivo and cultured enzyme-linked immunospot (ELISPOT) assays, we identified serotype-specific T cell epitopes within the four DENV serotypes in healthy adult donors from Sri Lanka. We identified T cell responses to 19 regions of the four DENV serotypes. Six peptides were from the NS2A region and four peptides were from the NS4A region. All immune donors responded to peptides of at least two DENV serotypes, suggesting that heterologous infection is common in Sri Lanka. Eight of 20 individuals responded to at least two peptides of DENV-4, despite this serotype not being implicated previously in any of the epidemics in Sri Lanka. The use of these regions to determine past and current infecting DENV serotypes will be of value to characterize further the dynamics of silent dengue transmission in the community. In addition, these T cell responses to these regions could be used to characterize DENV serotype-specific immune responses and thus possibly help us to understand the immune correlates of a protective immune response.
Pigment epithelium‐derived factor increases in type 2 diabetes after treatment with metformin
Authors: Akın Şafak , Aksoy Duygu Yazgan , Çınar Neşe , Aydın Kadriye , Karaağaoğlu Ergun , Arıyürek Macit , Gülçelik Neşe Ersöz , Usman Aydan , Gürlek Alper
Published: January 2012

Objective

Pigment epithelium‐derived factor (PEDF) has anti‐angiogenic, immunomodulatory and anti‐inflammatory properties. In addition to the significant role it plays in reducing diabetic complications, PEDF is now used in the treatment of certain cancers. It possibly plays a role in insulin resistance cases, too. However, whether metformin treatment has any significant effects on PEDF levels is not known. In this study, we investigated the regulation of PEDF in type 2 diabetes in relation to fat mass and insulin resistance before and after the use of metformin for treatment.

Design

Prospective cohort study.

Subjects

Thirty‐six patients with newly diagnosed type 2 diabetes and 33 healthy individuals.

Measurements

Baseline weight, waist circumference (WC), fasting (FPG) and postprandial (PPPG) glucose, insulin, HbA1c, HOMA, PEDF and total/truncal fat mass were determined both in the diabetic and control subjects. Procedures were repeated in the diabetic group after a 6‐month metformin treatment.

Results

Baseline FPG, PPPG, HbA1c, HOMA, weight, WC and truncal fat mass were higher in patients with diabetes whereas PEDF levels were found to be comparable with the controls. We completed the study with 31 of the 36 patients with diabetes we had selected for the study. We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0·002) after the metformin treatment. On the other hand, no significant correlation was observed between the change in PEDF levels and the clinical and laboratory findings.

Conclusion

Our study is the first to identify a metformin‐related increase in PEDF levels in diabetes. The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control. Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.
Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy
Authors: Vaisman Fernanda , Momesso Denise , Bulzico Daniel A. , Pessoa Cencita H. C. N. , Dias Fernando , Corbo Rossana , Vaisman Mário , Tuttle R. Michael
Published: January 2012

Objective

To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re‐stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States.

Design

Retrospective chart review.

Patients

Five hundred and six patients with DTC followed for a median of 10 years after total thyroidectomy and RAI remnant ablation at a major cancer centre in Brazil.

Measurements

Final clinical outcomes were assessed based on American Joint Cancer Committee (AJCC)/Union Internationale Contre le Cancer (UICC) staging, ATA risk stratification and response to therapy assessment (excellent, acceptable, biochemical incomplete and structural incomplete).

Results

The AJCC/UICC staging system did not adequately stratify patients with regard to the risk of recurrence/persistent disease. However, the ATA system demonstrated a 13% risk of recurrent/persistent disease in low‐risk patients, 36% in intermediate risk patients, and 68% in high‐risk patients. Furthermore, an excellent response to therapy decreased the risk of recurrent/persistent disease to 1·4%. At the time of final follow‐up, 34% of the biochemical incomplete response patients had been re‐classified as having no evidence of disease (NED) without having received any additional therapy beyond continue levothyroxine suppression. Conversely, even after additional therapies, only 9% of the patients with an incomplete structural response were eventually re‐classified as NED.

Conclusions

These data validate the ATA risk classification as an excellent initial predictor of recurrent/persistent disease and confirm the clinical utility of the MSKCC dynamic risk assessment system in a cohort of patients evaluated and treated outside the United States.
Aggregate stability and physical protection of soil organic carbon in semi‐arid steppe soils
Authors: Wiesmeier M. , Steffens M. , Mueller C. W. , Kölbl A. , Reszkowska A. , Peth S. , Horn R. , Kögel‐Knabner I.
Published: January 2012

Spatial inaccessibility of soil organic carbon (SOC) for microbial decay within soil aggregates is an important stabilization mechanism. However, little is known about the stability of aggregates in semiarid grasslands and their sensitivity to intensive grazing. In this study, a combined approach using soil chemical and physical analytical methods was applied to investigate the effect of grazing and grazing exclusion on the amount and stability of soil aggregates and the associated physical protection of SOC. Topsoils from continuously grazed (CG) and ungrazed sites where grazing was excluded from 1979 onwards (UG79) were sampled for two steppe types in Inner Mongolia, northern China. All samples were analysed for basic soil properties and separated into free and aggregate‐occluded light fractions (fLF, oLF) and mineral‐associated fractions. Tensile strength of soil aggregates was measured by crushing tests. Undisturbed as well as artificially compacted samples, where aggregates were destroyed mechanically by compression, were incubated and the mineralization of SOC was measured. For undisturbed samples, the cumulative release of CO2‐C was greater for CG compared with UG79 for both steppe types. A considerably greater amount of oLF was found in UG79 than in CG soils, but the stabilities of 10–20‐mm aggregates were less for ungrazed sites. Compacted samples showed only a slightly larger carbon release with CG but a considerably enhanced mineralization with UG79. We assume that the continuous trampling of grazing animals together with a smaller input of organic matter leads to the formation of mechanically compacted stable ‘clods’, which do not provide an effective physical protection for SOC in the grazed plots. In UG79 sites, a greater input of organic matter acting as binding agents in combination with an exclusion of animal trampling enhances the formation of soil aggregates. Thus, grazing exclusion promotes the physical protection of SOC by increasing soil aggregation and is hence a management option to enhance the C sequestration potential of degraded steppe soils.
Pilot‐scale field validation of the long electrode electrical resistivity tomography method
Authors: Rucker Dale F. , Crook Nigel , Glaser Danney , Loke Meng H.
Published: January 2012

A validation experiment, carried out in a scaled field setting, was attempted for the long electrode electrical resistivity tomography method in order to demonstrate the performance of the technique in imaging a simple buried target. The experiment was an approximately 1/17 scale mock‐up of a region encompassing a buried nuclear waste tank on the Hanford site. The target of focus was constructed by manually forming a simulated plume within the vadose zone using a tank waste simulant. The long electrode results were compared to results from conventional point electrodes on the surface and buried within the survey domain. Using a pole‐pole array, both point and long electrode imaging techniques identified the lateral extents of the pre‐formed plume with reasonable fidelity but the long electrode method was handicapped in reconstructing vertical boundaries. The pole‐dipole and dipole‐dipole arrays were also tested with the long electrode method and were shown to have the least favourable target properties, including the position of the reconstructed plume relative to the known plume and the intensity of false positive targets. The poor performance of the pole‐dipole and dipole‐dipole arrays was attributed to an inexhaustive and non‐optimal coverage of data at key electrodes, as well as an increased noise for electrode combinations with high geometric factors. However, when comparing the model resolution matrix among the different acquisition strategies, the pole‐dipole and dipole‐dipole arrays using long electrodes were shown to have significantly higher average and maximum values within the matrix than any pole‐pole array. The model resolution describes how well the inversion model resolves the subsurface. Given the model resolution performance of the pole‐dipole and dipole‐dipole arrays, it may be worth investing in tools to understand the optimum subset of randomly distributed electrode pairs to produce maximum performance from the inversion model.
A novel immunohistochemical sequential multi‐labelling and erasing technique enables epitope characterization of bone marrow pericytes in primary myelofibrosis
Authors: Madelung Ann , Bzorek Michael , Bondo Henrik , Zetterberg Eva , Bjerrum Ole Weis , Hasselbalch Hans Carl , Scheding Stefan , Ralfkiaer Elisabeth
Published: January 2012

Madelung A, Bzorek M, Bondo H, Zetterberg E, Bjerrum O W, Hasselbalch H C, Scheding S & Ralfkiaer E  (2012) Histopathology 60, 554–560 A novel immunohistochemical sequential multi‐labelling and erasing technique enables epitope characterization of bone marrow pericytes in primary myelofibrosis

Aim:  In Philadelphia (Ph)‐negative chronic myeloproliferative neoplasms, increased microvascular density, bizarre vessel architecture and increased number of pericytes are among the distinct histopathological features. The aim of this study was to characterize bone marrow pericytes in primary myelofibrosis (PMF) using a novel multi‐labelling immunohistochemical technique.

Methods and results:  Bone marrow biopsies from a normal donor (n = 1) and patients with PMF (n = 3) were subjected to an immunohistochemical sequential multi‐labelling and erasing technique (SE‐technique). Antigens of interest in the first and/or second layer were detected with an immunoperoxidase system and visualized with aminoethylcarbazole. After imaging, erasing and blocking of immunoreagents, the slides were stained with a traditional double immunolabelling procedure. In addition, we applied a Photoshop® colour palette, creating a single composite image of the sequential staining procedures. We successfully applied four layers of antibodies on one slide using CD146, smooth muscle actin, CD34, CD271 and Ki67 in different combinations. The SE‐technique significantly improves morphological and phenotypical studies in bone marrow specimens.

Conclusions:  To our knowledge, the SE‐technique is the first to multi‐label antigens, identifying vessel and pericyte architecture in bone marrow by light microscopy. This technique may unravel novel aspects of the composition of the microvessel structures in patients with PMF and related neoplasms.
Ecology of the microbiome of the infected root canal system: a comparison between apical and coronal root segments
Authors: Özok A. R. , Persoon I. F. , Huse S. M. , Keijser B. J. F. , Wesselink P. R. , Crielaard W. , Zaura E.
Published: January 2012

Özok AR, Persoon IF, Huse SM, Keijser BJF, Wesselink PR, Crielaard W, Zaura E. Ecology of the microbiome of the infected root canal system: a comparison between apical and coronal root segments. International Endodontic Journal, 45, 530–541, 2012.

Aim  To evaluate the microbial ecology of the coronal and apical segments of infected root canal systems using a complete sampling technique and next‐generation sequencing.

Methodology  The roots of 23 extracted teeth with apical periodontitis were sectioned in half, horizontally, and cryo‐pulverized. Bacterial communities were profiled using tagged 454 pyrosequencing of the 16S rDNA hypervariable V5‐V6 region.

Results  The sequences were classified into 606 taxa (species or higher taxon), representing 24 bacterial phyla or candidate divisions and one archaeal phylum. Proteobacteria were more abundant in the apical samples (P < 0.05), whilst Actinobacteria were in significantly higher proportions in the coronal samples. The apical samples harboured statistically significantly more taxa than the coronal samples (P = 0.01) and showed a higher microbial diversity. Several taxa belonging to fastidious obligate anaerobes were significantly more abundant in the apical segments of the roots compared with their coronal counterparts.

Conclusions  Endodontic infections are more complex than reported previously. The apical part of the root canal system drives the selection of a more diverse and more anaerobic community than the coronal part. The presence of a distinct ecological niche in the apical region explains the difficulty of eradication of the infection and emphasizes the need for new treatment approaches to be developed.