bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic dust exposure increases mast cell tryptase in bronchoalveolar lavage fluid and airway epithelium of heaves horses
Authors: Dacre K. J. , McGorum B. C. , Marlin D. J. , Bartner L. R. , Brown J. K. , Shaw D. J. , Robinson N. E. , Deaton C. , Pemberton A. D.
Published: October 2007

Background
Mast cell degranulation is believed to act as a key event in initiating and maintaining airway response to allergen challenge in human asthma. It is hypothesized that the mast cell may play a similar role in equine heaves, which shares many similarities with occupational dust‐induced asthma.

Objective
The aim of this study was to quantify the mast cell proteinase tryptase in bronchoalveolar lavage fluid (BALF) from control and heaves‐susceptible horses and to investigate tryptase mRNA and protein expression in pulmonary mast cells.

Methods
Equine BALF tryptase concentrations were determined by ELISA from control and heaves‐susceptible horses pre and post 24 h hay/straw challenge (HSC). Tryptase mRNA and protein expression were investigated by quantitative PCR and immunohistochemistry in bronchial and bronchiolar tissue samples of control and heaves‐susceptible horses.

Results
Both control and heaves‐susceptible horses had significantly increased BALF tryptase concentrations following HSC (P=0.003 and 0.034, respectively). Increased numbers of tryptase‐expressing intra‐epithelial mast cells were demonstrated in heaves horses, but not controls, following challenge (P=0.02). Bronchiolar tissue from heaves horses removed from challenge contained significantly lower tryptase transcripts than that from control horses (P=0.02).

Conclusion
Mast cell degranulation and tryptase release into the airways occur following HSC of control and heaves‐susceptible horses. The greater number of mast cells available in the bronchiolar epithelium of heaves horses may be clinically significant in the pulmonary inflammatory response of heaves.
CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma
Authors: Konjević G. , Jović V. , Vuletić A. , Radulović S. , Jelić S. , Spužić I.
Published: October 2007

Background  The few chemoimmunotherapy trials that together with dacarbazine (DTIC) and interferon‐α 2a (IFNα), include retinoic acid (RA), did not include detailed immunological evaluation of functional and phenotypic natural killer (NK) cell characteristics, and have shown contradictory clinical results.

Materials and methods  Malignant melanoma (MM) patients undergoing phase II‐randomized chemoimmunotherapy trials were treated with DTIC, IFNα (Hoffmann‐La Roche) (group A, n = 31), and with DTIC, IFNα and 13‐cis‐RA (Isotretinoin, Hoffmann‐La Roche, Basel, Switzerland) (group B, n = 29). Patients and 42 healthy controls were evaluated by FACS flow analyses for CD3/CD56/CD69 positive cells, NK cytotoxicity in fresh peripheral blood lymphocytes (PBL) and for interferon regulatory factor‐1 mRNA expression by reverse transcriptase polymerase chain reaction in treated PBL.

Results  The addition of RA to a DTIC‐IFN regime did not bring any therapeutical benefit in terms of response or survival. Immunological follow‐up on days 1, 6 and 27 of each therapy cycle shows a significant increase in NK cell activity in both groups, only on day 6 of the first cycle, while CD69+CD56+ expression increased significantly on day 6 of each therapy cycle, in both groups. Evaluation of the dynamics of expression of IRF‐1 of in vitro treated PBL, shows its strong and prompt up‐regulation by IFNα and synergistic effect of IFNα and RA combination.

Conclusion  The dynamics of the increase in CD69 early activation antigen expression on CD56+ NK cells is systematic and serial with the increase being significantly higher on day six of the first cycle in group B patients with clinical response, compared to those without, indicating possible predictive value of CD69 expression for clinical response to chemoimmunotherapy.
Effect of parental hypertension and/or parental diabetes on hypertension in Taiwanese diabetic patients
Authors: Tseng C. H.
Published: October 2007

Background  Both type 2 diabetes mellitus (T2DM) and hypertension aggregate in families. It is a common thought that diabetic patients with parental diabetes and/or parental hypertension are more likely to develop hypertension. This study evaluated the separate and joint effects of parental hypertension and parental diabetes on the prevalence of hypertension in patients with T2DM.

Materials and methods  A total of 89 956 patients from a national cohort were interviewed by telephone. Information about age, sex, onset age of diabetes, body height, body weight, systolic (SBP) and diastolic blood pressure (DBP), smoking, hypertension, and paternal and maternal history of diabetes and hypertension were obtained. Hypertension was defined in two ways: (1) a positive history; or (2) a positive history or a reported SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg in patients without a hypertension history.

Results  While analysed separately in logistic models, both parental diabetes and parental hypertension were positively associated with hypertension. However, when both were analysed together, only parental hypertension was positively associated with hypertension, with paternal and maternal hypertension exerting a similar effect of an approximately 2·5‐fold higher risk. While considering the effect of parental hypertension, both paternal and maternal diabetes was significantly associated with a lower risk of hypertension with odds ratios of approximately 0·8. Parental hypertension was also significantly associated with increased SBP and DBP; and parental diabetes with lower values in multiple linear regression.

Conclusions  Parental hypertension is strongly associated with hypertension. However, parental diabetes may be protective if the effect of parental hypertension is considered.
Linking the occurrence of brook trout with isolation and extinction in small Boreal Shield lakes
Authors: BERTOLO ANDREA , MAGNAN PIERRE , PLANTE MICHEL
Published: October 2007

1. We surveyed 62 Canadian Shield lakes (<50 ha) to determine the relationship between factors related to isolation and extinction and the occurrence of brook trout (BT) (Salvelinus fontinalis), for which local extinctions have been documented over the last century in half of the lakes.

2. Logistic regression and information–theoretic model selection were used to determine the importance for the occupancy of BT of (i) isolation factors (degree of lake connectivity and the proximity of source populations of BT in neighbouring bodies of water) and (ii) extinction factors (lake morphometry and trophic status, as proxies of the risk of lake anoxia; predation and competition; and flooding caused by beaver (Castor canadensis) dams, which could potentially increase the risk of anoxia).

3. Isolation factors were the best predictors of the absence of BT in these lakes. Among extinction factors, only the impact of beaver dams (as measured by an index of increased water level and mortality of shrubs and trees in the littoral zone) improved model fits. Beaver dams were present at the outlets of all study lakes, but extensive mortality of riparian trees and shrubs was more common in lakes where BT populations were extinct.

4. Taken together, these results suggest that recolonization is a major factor determining the occurrence of BT while flooding caused by beaver dams might contribute to BT extinction by increasing the likelihood of winterkill in these small lakes.
Factor VIII inhibitor bypassing activity (FEIBA) – addressing safety issues
Authors: ALEDORT L. M.
Published: October 2007

Summary.  Bypassing therapy is usually necessary to control or prevent bleeding episodes in patients with haemophilia A or B and high‐titre inhibitors. Factor VIII inhibitor bypassing activity (FEIBA) has a long history of successful use in the acute, surgical and prophylactic treatment settings, but safety concerns have made some reluctant to administer this bypassing agent. A review of the literature and clinical trial data show that FEIBA has a low prevalence of thrombosis, a low prevalence of anamnesis that does not impact haemostatic efficacy and an excellent record of pathogen safety and clinical tolerability.
Effect of activated antigen‐specific B cells on ES‐62‐mediated modulation of effector function of heterologous antigen‐specific T cells in vivo
Authors: Marshall Fraser A. , Watson Katherine A. , Garside Paul , Harnett Margaret M. , Harnett William
Published: October 2007

There is currently great interest in the idea of using helminth‐derived molecules for therapeutic purposes and indeed we have shown that ES‐62, a filarial nematode‐derived phosphorylcholine‐containing glycoprotein, significantly reduces the severity of arthritis in a murine model. Clearly, knowledge of mechanism of action is important when considering molecules for use in treating disease and although much is known regarding how ES‐62 interacts with the immune system, gaps in our understanding remain. A feature of filarial nematode infection is a defective, T helper 2 (Th2)‐polarized antigen‐specific T‐cell response and in relation to this we have recently shown that ES‐62 inhibits clonal expansion and modulates effector function towards a Th2 phenotype, of antigen‐specific T cells in vivo. ES‐62 is also known to directly modulate B‐cell behaviour and hence to determine whether it was mediating these effects on T cells by disrupting B–T‐cell co‐operation, we have investigated antigen‐specific responses using an adoptive transfer system in which traceable numbers of tg ovalbumin (OVA)‐specific T cells and hen egg lysozyme (HEL)‐specific B cells respond to a chemically coupled form of OVA–HEL that contains linked epitopes that promote cognate T‐ and B‐cell interactions. Surprisingly, these studies indicate that activated B cells restore T‐cell expansion and prevent Th2‐like polarization. However, ES‐62‐treated double cell transfer mice demonstrate a more generalized immunosuppression with reduced levels of Th1 and ‐2 type cytokines and antibody subclasses. Collectively, these results suggest that whilst ES‐62 can target B–T‐cell co‐operation, this does not promote polarizing of T‐cell responses towards a Th2‐type phenotype.
Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial
Authors: Nair P. N. R. , Duncan H. F. , Pitt Ford T. R. , Luder H. U.
Published: October 2007

Aim  To investigate the pulpal response to direct pulp capping in healthy human teeth with mineral trioxide aggregate (MTA) as against calcium hydroxide cement (Dycal®) as control.

Methodology  Twenty healthy human third molars had iatrogenic pulpotomy and direct pulp capping with MTA. Another 13 teeth were capped with Dycal® as controls. The teeth were restored, with IRM®, clinically reviewed and extracted after a number of pre‐determined intervals (1 week, 1 month and 3 months). The specimens were fixed, decalcified, subdivided axially into two halves in the oro‐buccal (lingual–buccal) plane, embedded in plastic, serial sectioned and evaluated qualitatively and quantitatively by correlative light and transmission electron microscopy with appropriate statistical evaluation of the quantitative data.

Results  Iatrogenic pulpal wounds treated with MTA were mostly free from inflammation after 1 week and became covered with a compact, hard tissue barrier of steadily increasing length and thickness within 3 months following capping. Control teeth treated with Dycal® revealed distinctly less consistent formation of a hard tissue barrier that had numerous tunnel defects. The presence of pulpal inflammation up to the longest observation period (3 months) after capping, was a common feature in Dycal® specimens.

Conclusions  The MTA was clinically easier to use as a direct pulp–capping agent and resulted in less pulpal inflammation and more predictable hard tissue barrier formation than Dycal®. Therefore, MTA or equivalent products should be the material of choice for direct pulp capping procedures instead of hard setting calcium hydroxide cements.
Detecting the influence of climatic variables on species distributions: a test using GIS niche‐based models along a steep longitudinal environmental gradient
Authors: Costa Gabriel C. , Wolfe Christina , Shepard Donald B. , Caldwell Janalee P. , Vitt Laurie J.
Published: October 2007

Aim  To investigate the influence of climate variables in shaping species distributions across a steep longitudinal environmental gradient.

Location  The state of Oklahoma, south‐central United States.

Methods  We used Geographical Information Systems (GIS) niche‐based models to predict the geographic distributions of six pairs of closely related amphibian and reptile species across a steep longitudinal environmental gradient. We compared results from modelling with actual distributions to determine whether species distributions were primarily limited by environmental factors, and to assess the potential roles of competition and historical factors in influencing distributions.

Results  For all species pairs, GIS models predicted an overlap zone in which both species should occur, although in reality in some cases this area was occupied by only one of the species. We found that environmental factors clearly influence the distributions of most species pairs. We also found evidence suggesting that competition and evolutionary history play a role in determining the distributions of some species pairs.

Main conclusions  Niche‐based GIS modelling is a useful tool for investigating species distribution patterns and the factors affecting them. Our results showed that environmental factors strongly influenced species distributions, and that competition and historical factors may also be involved in some cases. Furthermore, results suggested additional lines of research, such as ecological comparisons among populations occurring inside and outside predicted overlap zones, which may provide more direct insight into the roles of competitive interactions and historical factors in shaping species distributions.
A study of the human hair structure with a Zernike phase contrast X‐ray microscope
Authors: YOUN HWA SHIK , SHIN TAE JOO
Published: October 2007

We have observed the internal structure of human hair shafts with a transmission Zernike phase contrast hard X‐ray microscope. Due to the high spatial resolution and the high contrast of the microscope, we could image scales, macrofibrils, medulla and melanin without staining. The structure of a black hair shaft is compared with that of a white one.
Noise‐induced systematic errors in ratio imaging: serious artefacts and correction with multi‐resolution denoising
Authors: WANG YU‐LI
Published: October 2007

Ratio imaging is playing an increasingly important role in modern cell biology. Combined with ratiometric dyes or fluorescence resonance energy transfer (FRET) biosensors, the approach allows the detection of conformational changes and molecular interactions in living cells. However, the approach is conducted increasingly under limited signal‐to‐noise ratio (SNR), where noise from multiple images can easily accumulate and lead to substantial uncertainty in ratio values. This study demonstrates that a far more serious concern is systematic errors that generate artificially high ratio values at low SNR. Thus, uneven SNR alone may lead to significant variations in ratios among different regions of a cell. Although correct average ratios may be obtained by applying conventional noise reduction filters, such as a Gaussian filter before calculating the ratio, these filters have a limited performance at low SNR and are prone to artefacts such as generating discrete domains not found in the correct ratio image. Much more reliable restoration may be achieved with multi‐resolution denoising filters that take into account the actual noise characteristics of the detector. These filters are also capable of restoring structural details and photometric accuracy, and may serve as a general tool for retrieving reliable information from low‐light live cell images.
A line‐scanning semi‐confocal multi‐photon fluorescence microscope with a simultaneous broadband spectral acquisition and its application to the study of the thylakoid membrane of a cyanobacterium Anabaena PCC7120
Authors: KUMAZAKI SHIGEICHI , HASEGAWA MAKOTO , GHONEIM MOHAMMAD , SHIMIZU YUGO , OKAMOTO KENJI , NISHIYAMA MASAYOSHI , OH‐OKA HIROZO , TERAZIMA MASAHIDE
Published: October 2007

We describe the construction and characterization of a laser‐line‐scanning microscope capable of detection of broad fluorescence spectra with a resolution of 1 nm. A near‐infrared femtosecond pulse train at 800 nm was illuminated on a line (one lateral axis, denoted as X axis) in a specimen by a resonant scanning mirror oscillating at 7.9 kHz, and total multi‐photon–induced fluorescence from the linear region was focused on the slit of an imaging polychromator. An electron‐multiplying CCD camera was used to resolve fluorescence of different colours at different horizontal pixels and fluorescence of different spatial positions in a specimen at different vertical pixels. Scanning on the other two axes (Y and Z) was achieved by a closed‐loop controlled sample scanning stage and a piezo‐driven objective actuator. The full widths at half maximum of the point‐spread function of the system were estimated to be 0.39–0.40, 0.33 and 0.56–0.59 μm for the X (lateral axis along the line‐scan), Y (the other lateral axis) and Z axes (the axial direction), respectively, at fluorescence wavelengths between 644 and 690 nm. A biological application of this microscope was demonstrated in a study of the sub‐cellular fluorescence spectra of thylakoid membranes in a cyanobacterium, Anabaena PCC7120. It was found that the fluorescence intensity ratio between chlorophyll molecules mainly of photosystem II and phycobilin molecules of phycobilisome (chlorophyll/phycobilin), in the thylakoid membranes, became lower as one probed deeper inside the cells. This was attributable not to position dependence of re‐absorption or scattering effects, but to an intrinsic change in the local physiological state of the thylakoid membrane, with the help of a transmission spectral measurement of sub‐cellular domains. The efficiency of the new line‐scanning spectromicroscope was estimated in comparison with our own point‐by‐point scanning spectromicroscope. Under typical conditions of observing cyanobacterial cells, the total exposure time became shorter by about 50 times for a constant excitation density. The improvement factor was proportional to the length of the line‐scanned region, as expected.
Verification of cell viability at progressively higher scanning forces using a hybrid atomic force and fluorescence microscope
Authors: BARNES C. A. , O'HAGAN B. M. G. , HOWARD C. V. , MCKERR G.
Published: October 2007

The prudent use of the atomic force microscope as a supra‐vital live cell imaging tool requires that cell viability must be determined before and after scanning. Complementary optical techniques in conjunction with the fluorescent dyes rhodamine‐123 and ethidium homodimer have been used within this study to determine cell viability after increasing loads are applied in contact mode. Guideline force ranges for five commonly cultured cell lines, human squamous carcinoma (A431), fibroblast, HeLa, Potorous tridactylis (PtK2) and rat intestinal epithelial (RIE) cells are given.
Improved lateral force calibration based on the angle conversion factor in atomic force microscopy
Authors: CHOI DUKHYUN , HWANG WOONBONG , YOON EUISUNG
Published: October 2007

A novel calibration method is proposed for determining lateral forces in atomic force microscopy (AFM), by introducing an angle conversion factor, which is defined as the ratio of the twist angle of a cantilever to the corresponding lateral signal. This factor greatly simplifies the calibration procedures. Once the angle conversion factor is determined in AFM, the lateral force calibration factors of any rectangular cantilever can be obtained by simple computation without further experiments. To determine the angle conversion factor, this study focuses on the determination of the twist angle of a cantilever during lateral force calibration in AFM. Since the twist angle of a cantilever cannot be directly measured in AFM, the angles are obtained by means of the moment balance equations between a rectangular AFM cantilever and a simple commercially available step grating. To eliminate the effect of the adhesive force, the gradients of the lateral signals and the twist angles as a function of normal force are used in calculating the angle conversion factor. To verify reliability and reproducibility of the method, two step gratings with different heights and two different rectangular cantilevers were used in lateral force calibration in AFM. The results showed good agreement, to within 10%. This method was validated by comparing the coefficient of friction of mica so determined with values in the literature.
Potential of ‘flat’ fibre evanescent wave spectroscopy to discriminate between normal and malignant cells in vitro
Authors: HAMMODY Z. , HULEIHEL M. , SALMAN A. , ARGOV S. , MOREH R. , KATZIR A. , MORDECHAI S.
Published: October 2007

The present study focuses on evaluating the potential of flattened AgClBr fibre‐optic evanescent wave spectroscopy (FTIR‐FEWS) technique for detection and identification of cancer cells in vitro using cell culture as a model system. The FTIR‐FEWS results are compared to those from FTIR‐microspectroscopy (FTIR‐MSP) method extensively used to identify spectral properties of intact cells. Ten different samples of control and malignant cells were measured in parallel by the above two methods. Our results show a significant similarity between the results obtained by the two methodologies. The absorbance level of Amide I/Amide II, phosphates and carbohydrates were significantly altered in malignant compared to the normal cells using both systems. Thus, common biomarkers such as Amide I/Amide II, phosphate and carbohydrate levels can be derived to discern between normal and cancer cells. However, marked differences are also noted between the two methodologies in the protein bands due to CH3 bending vibration (1480–1350 cm−1). The spectral differences may be attributed to the variation in the penetration depth of the two methodologies. The use of flattened fibre rather than the standard cylindrical fibre has several practical advantages and is considered as an important step towards in vivo measurements in real time, such as that of skin nevi and melanoma using special designs of fibre‐optic–based sensors.
Simultaneous false‐colour imaging of birefringence, extinction and transmittance at camera speed
Authors: KAMINSKY W. , GUNN E. , SOURS R. , KAHR B.
Published: October 2007

A polarized light imaging technique is introduced that simultaneously captures and unfolds transmittance, fast/slow axes directions and birefringence or linear dichroism from single camera exposures. The technique, based on the rotating polarizer method, is capable of sampling an object through polarizers at four different angles in a single image with the use of an image multiplexer. The range of possible applications is demonstrated with examples from the fields of biology, medicine, forensics and material sciences.
The effect of the polymerized bovine haemoglobin solution, Hb‐200, on endothelial function in isolated arterial rings from rats
Authors: PAWSON P. , GIBSON I. F. , DOWELL F. J.
Published: October 2007

Haemoglobin‐based oxygen carriers have been developed as ‘blood substitutes’. Early cross‐linked haemoglobins caused marked vasoconstriction, however, polymerized haemoglobin solutions, such as the bovine product haemoglobin glutamer‐200 (bovine) (Hb‐200), are said to have lesser vascular effects. The aim of this study was to quantify the effect of Hb‐200 on isolated rat arterial rings. The actions of Hb‐200 were investigated using rings of aorta and second‐order mesenteric arteries from female Wistar rats. The arterial rings were mounted for isometric tension recording. Addition of Hb‐200 (1 μm) to arterial rings, precontracted with phenylephrine (50–70% maximum phenylephrine‐induced tone), resulted in vasoconstriction. Addition of Hb‐200 to arteries precontracted with phenylephrine and relaxed with acetylcholine (1 μm) also caused contraction. Furthermore preincubation with Hb‐200 (1 μm) enhanced the response to phenylephrine (1 nmto 10 μm) and impaired acetylcholine‐induced relaxation (10 nmto 10 μm). Responses to Hb‐200 were similar to those in response to the nitric oxide (NO) synthase inhibitor,NG‐nitro‐l‐arginine methyl ester (l‐NAME, 100 μm), alone or in combination with Hb‐200. These data demonstrate that Hb‐200 has a significant vasoconstrictor effect similar tol‐NAME. Thus the vascular actions of Hb‐200 are consistent with activity as a NO scavenger. This may have implications for the clinical use of Hb‐200.
Selective microenvironmental effects play a role in shaping genetic diversity and structure in a Phaseolus vulgaris L. landrace: implications for on‐farm conservation
Authors: TIRANTI B. , NEGRI V.
Published: October 2007

Little is known about the organization of landrace diversity and about the forces that shape and maintain within‐ and among‐landrace population diversity. However, this knowledge is essential for conservation and breeding activities. The first aim of this study was to obtain some insight into how variation has been sculptured within a cultivated environment and to identify the loci that potentially underlie selective effects by using a Phaseolus vulgaris L. landrace case study whose natural and human environment and morpho‐physiological traits are known in detail. The second aim of this study was to define an appropriate on‐farm conservation strategy which can serve as a model for other populations. The farmers’ populations of this threatened landrace were examined with 28 single sequence repeat molecular markers. The landrace appears to be a genetically structured population in which substantial diversity is maintained at the subpopulation level (62% of the total variance). Evidence of locus‐specific selective effects was obtained for five of the 13 loci‐differentiating subpopulations. Their role is discussed. Our data suggest that a complex interaction of factors (differential microenvironmental selection pressures by farmers and by biotic and abiotic conditions, migration rate and drift) explains the observed pattern of diversity. Appropriate on‐farm conservation of a structured landrace requires the maintenance of the entire population.
Powers of discerning: challenges to understanding dispersal processes in natural populations
Authors: DYER RODNEY J.
Published: October 2007

In this issue of Molecular Ecology, authors Robledo‐Arnuncio & Garcia present a compelling approach for quantifying seed dispersal in plant populations. Building upon methods previously used for quantification of pollen dispersal, the authors not only examine the behaviour of the model with respect to sample sizes, dispersal distance, and the kurtosis of the dispersal function but also provide an empirical example using Prunus mahaleb.
Nuclear and chloroplast microsatellites reveal extreme population differentiation and limited gene flow in the Aegean endemic Brassica cretica (Brassicaceae)
Authors: EDH KRISTINA , WIDÉN BJÖRN , CEPLITIS ALF
Published: October 2007

Nuclear and chloroplast microsatellite markers were used to study population structure and gene flow among seven Cretan populations of the Aegean endemic plant species Brassica cretica (Brassicaceae). Both nuclear and chloroplast markers revealed exceptionally high levels of population differentiation (overall FST = 0.628 and 1.000, respectively) and relatively little within‐population diversity (overall HS = 0.211 and 0.000, respectively). Maximum‐likelihood estimates of directional migration rates were low among all pairs of populations (average Nm = 0.286). There was no evidence that differences in flower colour between populations had any influence on historical levels of gene flow. In addition, a haplotype network showed that all five chloroplast haplotypes found in the sample were closely related. Together, these results suggest that current patterns of diversification in B. cretica are mainly a result of genetic drift during the last half million years. The main conclusions from the present study are consistent with the prevailing hypothesis that plant diversification in the Aegean region is driven by random rather than adaptive differentiation among isolated populations.
The coup de grâce for the nested clade phylogeographic analysis?
Authors: PETIT RÉMY J.
Published: October 2007

Nested clade phylogeographic analysis (NCPA) has become a popular method for reconstructing the history of populations across species ranges. Ever since its invention in 1995, criticisms have been formulated, but the method, which has been regularly updated, continues to attract investigators. Molecular Ecology has published a large fraction of the literature on the topic — both pro and con. A recent study by Panchal and Beaumont (2007) finally allows a precise evaluation of the method by developing software that automates the somewhat complicated NCPA procedure. Using simulations of random‐mating populations, Panchal and Beaumont find a high frequency of false‐positives with their automated NCPA procedure (over 75%). These findings, which echo and amplify earlier warnings, appear serious enough to suggest to researchers to await further evaluation of the method. Although no other all‐encompassing method such as the NCAP currently exists to evaluate phylogeographic data sets, researchers have many alternative methods to test ever more refined hypotheses.
Maltose binding protein (MalE) interacts with periplasmic loops P2 and P1 respectively of the MalFG subunits of the maltose ATP binding cassette transporter (MalFGK2) from Escherichia coli/Salmonella during the transport cycle
Authors: Daus Martin L. , Berendt Susanne , Wuttge Steven , Schneider Erwin
Published: October 2007

The ATP binding cassette (ABC‐) transporter mediating the uptake of maltose/maltodextrins in Escherichia coli/Salmonella enterica serovar Typhimurium is one of the best characterized systems and serves as a model for studying the molecular mechanism by which ABC importers exert their functions. The transporter is composed of a periplasmic maltose binding protein (MalE), and a membrane‐bound complex (MalFGK2), comprising the pore‐forming hydrophobic subunits, MalF and MalG, and two copies of the ABC subunit, MalK. We report on the isolation of suppressor mutations within malFG that partially restore transport of a maltose‐negative mutant carrying the malK809 allele (MalKQ140K). The mutation affects the conserved LSGGQ motif that is involved in ATP binding. Three out of four suppressor mutations map in periplasmic loops P2 and P1 respectively of MalFG. Cross‐linking data revealed proximity of these regions to MalE. In particular, as demonstrated in vitro and in vivo, Gly‐13 of substrate‐free and substrate‐loaded MalE is in close contact to Pro‐78 of MalG. These data suggest that MalE is permanently in close contact to MalG‐P1 via its N‐terminal domain. Together, our results are interpreted in favour of the notion that substrate availability is communicated from MalE to the MalK dimer via extracytoplasmic loops of MalFG, and are discussed with respect to a current transport model.
The antimicrobial peptide‐sensing system aps of Staphylococcus aureus
Authors: Li Min , Cha David J. , Lai Yuping , Villaruz Amer E. , Sturdevant Daniel E. , Otto Michael
Published: October 2007

Staphylococcus aureus is a leading cause of hospital‐associated and, more recently, community‐associated infections caused by highly virulent methicillin‐resistant strains (CA‐MRSA). S. aureus survival in the human host is largely defined by the ability to evade attacks by antimicrobial peptides (AMPs) and other mechanisms of innate host defence. Here we show that AMPs induce resistance mechanisms in CA‐MRSA via the aps AMP sensor/regulator system, including (i) the d‐alanylation of teichoic acids, (ii) the incorporation of lysyl‐phosphatidylglycerol in the bacterial membrane and a concomitant increase in lysine biosynthesis, and (iii) putative AMP transport systems such as the vraFG transporter, for which we demonstrate a function in AMP resistance. In contrast to the aps system of S. epidermidis, induction of the aps response in S. aureus was AMP‐selective due to structural differences in the AMP binding loop of the ApsS sensor protein. Finally, using a murine infection model, we demonstrate the importance of the aps regulatory system in S. aureus infection. This study shows that while significant interspecies differences exist in the AMP–aps interaction, the AMP sensor system aps is functional and efficient in promoting resistance to a variety of AMPs in a clinically relevant strain of the important human pathogen S. aureus.
Comparison of mathematical methods for calculating colonic compliance in humans: power exponential, computer‐based and manual linear interpolation models
Authors: Floyd B. N. I. , Camilleri M. , Andresen V. , Esfandyari T. , Busciglio I. , Zinsmeister A. R.
Published: October 2007

Abstract Measuring compliance allows differentiation of sensory changes from changes in thresholds because of altered compliance. As compliance of the colorectum is sigmoidal, a power exponential analysis was recommended. We aimed to develop and validate simpler measurements of compliance. Forty subjects (23 female, 17 male) underwent colonic barostat procedures comparing dronabinolvsplacebo. Results of the effects on compliance were reported elsewhere. Compliance was determined as volume response to pressures ranging from 0 to 36 mmHg. Pressures corresponding to 10%, 50% and 90% (Pr10, Pr50 and Pr90) of maximum volume at 36 mmHg were estimated using a power exponential model, computer‐based and manual linear interpolation. Data were compared and concordance evaluated. Pr50 and Pr90 were not significantly different by all methods for baseline and post‐treatment. Respectively, concordance correlation coefficients were: pretreatment, 0.879, 0.464 and post‐treatment, 0.879, 0.623. There is larger variation in Pr10 comparing all methods and manual calculations allow for the closest fit to the data. Concordance correlation coefficients were pretreatment = 0.189 and post‐treatment = 0.322. There were no gender differences in compliance measurements. Results of compliance are highly concordant amongst all models. However, computer‐based or manual interpolations appear superior to power exponential models for estimating Pr10.
Calcium‐binding protein secretagogin‐expressing neurones in the human hippocampus are largely resistant to neurodegeneration in Alzheimer's disease
Authors: Attems J. , Preusser M. , Grosinger‐Quass M. , Wagner L. , Lintner F. , Jellinger K.
Published: October 2007

The pathological findings in Alzheimer's disease (AD) are partly attributed to alterations in calcium‐binding protein (CBP) functions. We showed previously that immunoreactivity of secretagogin, a recently cloned CBP, in the human hippocampus is restricted to pyramidal neurones and that the amount of immunoreactive neurones does not differ between AD cases and controls. In this study we investigate the influence of hippocampal tau pathology on secretagogin expression in more details. The study group consisted of 26 cases with different degrees of neuropathologically confirmed AD pathology. Sections were incubated separately with secretagogin‐ and tau‐specific antibodies, respectively. The amount of immunoreactive neurones and integral optical densities were assessed. In addition, double immunofluorescence for both secretagogin and tau was performed. No difference with respect to secretagogin immunoreactivity was observed in different stages of AD pathology, and similarly no significant associations were seen between the amount of secretagogin and tau immunoreactivity in the different hippocampal subfields. Double immunofluorescence revealed that both proteins rarely colocalize because only 5.3% of tau and 2.9% of secretagogin immunoreactive neurones, respectively, showed colocalization. Because there are no differences in the amount of hippocampal secretagogin expression between AD cases and controls (as we have shown previously), the lack of an association between the amount of secretagogin expression and tau burden together with the low frequency of colocalization of tau and secretagogin in the human hippocampus, suggest that secretagogin‐expressing neurones are largely resistant to neurodegeneration in AD.
Expression of SoxE and SoxD genes in human gliomas
Authors: Schlierf B. , Friedrich R. P. , Roerig P. , Felsberg J. , Reifenberger G. , Wegner M.
Published: October 2007

Members of group E and group D of the Sox gene family function as important transcriptional regulators of glial development in the central nervous system. Here, we have examined Sox gene expression in 60 human primary gliomas. Transcripts from each of the six group E and group D genes were expressed in gliomas of various types and malignancy grades, but with significant differences. SOX5, SOX9 and SOX10 were generally expressed at levels similar to or below those in adult brain tissue. In contrast, many oligodendrogliomas exhibited upregulation of SOX6, SOX8 and SOX13. Furthermore, loss of heterozygosity on chromosomal arms 1p and 19q was associated with significantly higher SOX8 mRNA levels. Low‐grade astrocytomas, but not glioblastomas, also showed elevated SOX8 transcript levels. Taken together, the expression pattern of Sox genes in gliomas is heterogeneous and overall compatible with the less differentiated state of glioma cells as compared with their normal adult counterparts. Despite their restricted expression in astrocytes and oligodendrocytes during normal development, none of the Sox genes was selectively expressed in tumours of the oligodendroglial or astrocytic lineage. This is compatible with an origin of gliomas from neuroepithelial stem or precursor cells.
Biogeographical and evolutionary patterns in the Macaronesian shield‐backed katydid genus Calliphona Krauss, 1892 (Orthoptera: Tettigoniidae) and allies as inferred from phylogenetic analyses of multiple mitochondrial genes
Authors: ARNEDO MIQUEL A. , OROMÍ PEDRO , MARTÍN DE ABREU SONIA , RIBERA CARLES
Published: October 2007

Abstract We investigated the phylogenetic patterns, evolutionary processes, and their taxonomic implications, of two closely related shield‐backed katydid genera endemic to the Macaronesian archipelagos: the monotypic Psalmatophanes Chopard, 1938 endemic to Madeira and Calliphona Krauss, 1892, which includes three species restricted to the Canary Islands. Two main hypotheses have been proposed to explain the origin and colonization pathways of these two genera: a single origin with subsequent sequential colonization of the islands, or three independent colonization waves from continental Africa. We used DNA sequence information from the mitochondrial genes cox1, tRNAleucine, rrnL and nad1 to infer phylogenetic relationships among Psalmatophanes and Calliphona species. Our results provide support for the independent colonization of Madeira and the Canary Islands, and suggest that Psalmatophanes is actually more closely related to the continental genus Tettigonia than to the Canarian representatives. Deep genetic divergence among Canarian species provides further support for the assignment of the Canarian species into two subgenera. Tree topology along with Bayesian‐based estimates of lineage age suggest a pattern of colonization from Tenerife to La Palma, and from Tenerife to Gran Canaria with subsequent dispersal to La Gomera. We report the first collection of a Calliphona specimen in the island of El Hierro, which molecular data suggest is a recent immigrant from La Gomera. We hypothesize that the patterns of distribution and genetic divergence exhibited by Calliphona in the Canary Islands are compatible with a taxon cycle process. Our results have further implications for the higher level phylogeny of the subfamily Tettigoniinae and suggest that some of the tribes as currently delimited may not correspond to natural groups.
Secondary erythromelalgia involving the ears probably preceding lupus erythematosus
Authors: Badeloe Sadhanna , Henquet Charles J. , Nieuwhof Chris M. G. , Frank Jorge
Published: October 2007

Secondary erythromelalgia is a rare disease characterized by burning pain, marked erythema, edema, and hyperthermia of the affected limbs. Secondary erythromelalgia can be associated with various systemic diseases. Here, we describe a patient who developed secondary erythromelalgia involving the ears and concomitant clinical and laboratory, probably, indicating the initial stage of a developing lupus erythematosus.
Treatment of lymphangioma circumscriptum with the intense pulsed light system
Authors: Thissen Carleine A. C. B. , Sommer Anja
Published: October 2007

Lymphangioma circumscriptum is a superficial lymphatic malformation presenting with grouped translucent vesicles that often contain blood. In the past, several treatment modalities have been described. Here, we report for the first time on treatment with an intense pulsed light source that led to good cosmetic results.
Porphyria cutanea tarda as rare cutaneous manifestation of hepatic metastases treated with interferon
Authors: Mosterd Klara , Henquet Charles , Frank Jorge
Published: October 2007

A 53‐year‐old woman with blistering on the hands was diagnosed with porphyria cutanea tarda (PCT). At that time, she was treated with interferon for liver metastasis of a pancreas tumor since 7 years. Although apparently rare, PCT has been described as possible cutaneous manifestation both of hepatic tumors and interferon treatment. Further, PCT can also be exacerbated by hepatitis C virus infection, alcohol, estrogens, HFE gene mutations predisposing for hereditary hemochromatosis, hexachlorobenzene, and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin. Therefore, it is important to keep in mind that the manifestation of PCT may be associated with distinct precipitating factors, which are briefly discussed here.
Lichen planus with bullous manifestation on the lip
Authors: Van Tuyll van Serooskerken Anne‐Moon , Van Marion Arienne M. W. , De Zwart‐Storm Eugene , Frank Jorge , Poblete‐Gutiérrez Pamela
Published: October 2007

A 75‐year‐old Caucasian female with a previous history of cutaneous lichen planus (LP) developed vesiculae and blisters on the lip. This special variant of oral LP is very rare and has to be distinguished from LP pemphigoides, bullous pemphigoid, pemphigus vulgaris, erythema multiforme, and herpes simplex virus infection. To date, there are only few reports on bullous oral LP on the lower lip. Although treatment is difficult, we successfully applied a topical combination of tretinoin 0.025% and triamcinolone 0.1%.
Cutaneous granulomas in rheumatoid arthritis
Authors: Collaris Esther J. H. , Van Marion Ariënne M. W. , Frank Jorge , Poblete‐Gutiérrez Pamela
Published: October 2007

A 57‐year‐old man with rheumatoid arthritis and myasthenia gravis developed an asymptomatic erythematous plaque on his nose and skin‐colored nodules on the elbows. Histopathological examination was suggestive of palisaded neutrophilic granulomatous dermatitis (PNGD). PNGD is a rather uncommon cutaneous finding in different collagen vascular disorders that can manifest with a broad range of clinical symptoms and histological signs. Based on the case report of the patient described here, we briefly discuss what is currently known about this disease.
Multicentric reticulohistiocytosis: case report
Authors: De Zwart‐Storm Eugene A. , Van Marion Ariënne M. W. , Gorter Simone L. , Frank Jorge , Kelleners‐Smeets Nicole W. J.
Published: October 2007

A 64‐year‐old woman developed slowly expanding asymptomatic red bumps on the hands and in the face since 1 year. Histopathological examination showed mononucleated and multinucleated giant cells with a characteristic “ground glass” appearance. Based on the clinical and histopathological findings, we made the diagnosis of multicentric reticulohistiocytosis (MRH). This rare variant of histiocytosis was described for the first time in 1950. Clinically, the disorder is characterized by papulonodular cutaneous lesions, and a severe and often destructive arthropathy. The reticulohistiocytoses are a rare group of closely related non‐Langerhans cell histiocytosis that most commonly manifest in adults. Because MRH can be associated with an underlying malignancies, and an interdisciplinary examination and regimen of these patients is advisable.
Onycholysis associated with subungual manifestation of barber's hair sinus
Authors: Nagtzaam Ivo F. , Van Der Velden Jaap J. A. J. , Kelleners‐Smeets Nicole W. J. , Frank Jorge
Published: October 2007

A female hairdresser presented with hair fragments embedded under her fingernails in association with yellow‐brownish discoloration and distal detachment of the nails. Based on these findings, we made the diagnosis of subungual barber's hair sinus with onycholysis. To our knowledge, this unique clinical picture has not been reported previously. A detailed medical history revealed several risk factors that might have contributed to the disease. Here, we briefly review what is known about barber's hair sinus, an occupational disease that is usually encountered in male hairdressers and only rarely manifests in women.
Severe chronic urticaria is associated with elevated plasma levels of D‐dimer
Authors: Asero R. , Tedeschi A. , Riboldi P. , Griffini S. , Bonanni E. , Cugno M.
Published: October 2007

Background:  Patients with chronic urticaria (CU) frequently show signs of thrombin generation as a result of the activation of the extrinsic pathway of coagulation and signs of fibrinolysis as shown by slightly increased mean D‐dimer plasma levels. Here, we studied patients with severe CU to see whether the activation of coagulation and fibrinolysis parallels the severity of the disease.

Methods:  Eight consecutive patients with severe exacerbations of CU and 13 with slight CU were studied. Plasma prothrombin fragment F1+2 as well as D‐dimer were measured by ELISA. Serum histamine‐releasing activity was assessed by basophil histamine release assay. Seventy‐four normal subjects were used as controls.

Results:  In patients with severe CU, median levels of both D‐dimer (11.20 nmol/l) and F1+2 (592 pmol/l) largely exceeded those found in patients with slight CU [D‐dimer: 2.66 nmol/l (P = 0.001) and F1+2: 228 pmol/l (P = 0.003)] and in normal subjects [D‐dimer: 1.41 nmol/l (P = 0.0001) and F1+2: 159 pmol/l (P = 0.0001)]. Sera from 25% of patients with severe CU and 31% of those with slight CU, but from none of normal subjects, showed in vitro histamine‐releasing activity. D‐dimer and F1+2 levels were significantly correlated each other (r = 0.64, P = 0.002) and with CU severity score (r = 0.80–0.90, P = 0.0001), but no correlation was observed between serum histamine‐releasing activity and coagulation parameters or severity score.

Conclusions:  Severe exacerbations of CU are associated with a strong activation of coagulation cascade and fibrinolysis. Whether this activation is the cause of CU or acts as an amplification system is still a matter of debate.