bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of an iodine treatment on the structure and physical properties of Bombyx mori silk fibroin fiber
Authors: Khan Majibur Rahman , Gotoh Yasuo , Miura Mikihiko , Morikawa Hideaki , Nagura Masanobu
Published: October 2006

Silk fibroin (SF) fiber from the Bombyx mori silkworm was treated with a 1.23 N iodine/potassium iodide (I2–KI) aqueous solution, and the structure and physical properties were investigated to elucidate the effects of the iodine treatment. The SF fiber absorbed polyiodide ions such as I and I by immersion in the I2–KI solution, and the weight gain of the SF fiber increased with the treatment time; it became saturated at about 20 wt % after 40 h. The results of the weight gain, Fourier transform infrared spectroscopy, and X‐ray diffraction measurements suggested that polyiodide ions mainly entered the amorphous region. Moreover, a new sharp reflection in the meridional direction, corresponding to a period of 7.0 Å, was observed and indicated the possibility of the formation of a mesophase structure of β‐conformation chains. Dynamic viscoelastic measurements showed that the molecular motion of the crystalline regions at about 220 °C was enhanced and shifted to lower temperature by the introduction of polyiodide ions. This indicated that the iodine component weakened the hydrogen bonding between the SF molecules forming the β‐sheet structure and caused molecular motion of the crystal to occur more easily with heating. With heating above 270 °C, the iodine component introduced intermolecular crosslinking to SF, and the melt flow of the sample was inhibited. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3418–3426, 2006
Diversity in fertility patterns in Guatemala
Authors: De Broe Sofie , Hinde Andrew
Published: October 2006

This study investigates urban and rural fertility trends in Guatemala up to 2002. It also aims to establish, using the theory of diffusion as its theoretical framework, the extent to which ethnicity and ethnic diversity are associated with geographical patterns in local‐level fertility after controlling for socio‐economic indicators. Data from the Demographic and Health Surveys of 1987, 1995–96 and 1998–99, the National Maternal and Child Health Survey of 2002 and the Census of 2002 were used. P/F ratios were calculated and used as an analytical tool and quality control measure of the data in order to establish the timing of changes in fertility patterns as measured by age‐specific fertility rates (ASFRs) based on exact exposure in four‐year periods from 1972 to 2002. Finally, the 2002 census data were used to analyse and model fertility at the municipio‐level using ordinary least squares regression. The results suggest a steady but very slow decline in fertility from 1972 until the mid‐1990s. Both the P/F ratios and ASFRs calculated using the Maternal and Child Health Survey and Census of 2002 show a sharp decline in fertility since 1998. The regression results for the census data suggest an independent and significant effect of ‘proportion of indigenous people’ and an almost significant effect of ethnic diversity on fertility at the municipio‐level. The very slow decline in fertility in Guatemala until fairly recently can be attributed to the fact that Guatemala has been lagging behind in terms of socio‐economic development and the additional challenge of having a culturally very diverse and segregated population, preventing the spread of modern reproductive ideas and behaviour. The accelerated fertility decline since the end of the 1990s seems likely to be associated with the widespread availability and increased uptake of family planning following declining fertility desires among its indigenous population. Copyright © 2006 John Wiley & Sons, Ltd.
Transnational citizens or circulating semi‐proletarians? A study of migration circulation between Sweden and Asia, Latin America and Africa between 1968 and 2002
Authors: Tollefsen Aina , Lindgren Urban
Published: October 2006

Theoretically significant research on transnational migrations has usually been based on in‐depth qualitative studies with detailed case study data linked to specific contexts. The concept of transnationalism has been used to capture and theorise enduring and complex interchanges of people, things and ideas between places, regions and/or countries, that are separated by borders, and usually by large physical distances. Transnationalism has also been linked to accounts of intense forms of international migration under globalisation, often in contexts of unequal power relations. Rather few studies have tried to grasp the phenomenon in larger samples, examining its importance and characteristics over time in different migratory contexts. While sharing theoretical and epistemological understandings from the transnational research field, this paper explores the phenomenon by analysing a comprehensive set of quantitative data on long‐distance frequent movers between Sweden and Asia, Latin America and Africa. By looking at the most mobile of all migrants in this South–North context, the paper explores the characteristics and scope of transnational migrations. The analyses show that transnational circulators, defined here as individuals who have migrated three times or more between Sweden and these regions, constitute a very small proportion of all South–North migrants over a 35‐year period. They are more likely than other groups to be highly educated, male, low‐income earners and Swedish citizens. These results contrast with other studies where transnational mobility of the highly skilled is often associated with successful career migration and high income groups. The conclusion of this paper is that, despite the high qualification level of circulators, long‐distance circulation between Sweden and the global South is associated with negative income and labour market situations. The paper also questions the relevance of the concept of transnationalism itself in this specific context. Copyright © 2006 John Wiley & Sons, Ltd.
Fertility transition in Ghana: looking back and looking forward
Authors: Agyei‐Mensah Samuel
Published: October 2006

It is widely accepted that while the fertility transition is underway in sub‐Saharan Africa, the pattern of change differs widely in both time and space. This paper examines the case of Ghana, regarded as the vanguard in the West African fertility transition. Based largely on analyses of Demographic and Health Survey data as well as localised studies, significant patterns emerge. One puzzling finding is that the increase in modern contraception usage has not kept pace with the declines in fertility. The paper suggests that this mismatch can be explained either by an increase in induced abortions, reduced exposure to sexual relations (perhaps due to HIV), or misreporting of contraceptive use. The paper also highlights the considerable geographical diversity in the ongoing fertility transition. The Northern region is still in the pre‐transition stage, with little decline in fertility to date. In contrast, the pace of decline has been very rapid in the Greater Accra region. The factors underlying these patterns and the future trajectory of the fertility transition are discussed. It is argued that the fertility transition may be more leisurely in the near future than in the recent past. Among the factors working against future fertility decline are the stability in the infant mortality rate, the stall in fertility desires, and the low patronage of modern contraceptives especially in rural areas. Copyright © 2006 John Wiley & Sons, Ltd.
Understanding dual‐track urbanisation in post‐reform China: conceptual framework and empirical analysis
Authors: Shen Jianfa
Published: October 2006

This paper examines dual‐track urbanisation in China, consisting of spontaneous urbanisation and state‐sponsored urbanisation. The paper first develops a consistent interpretative framework of urbanisation in pre‐reform and post‐reform China. The key components in the framework include the mode of industrialisation, central and local states, urban and rural economies, urban and rural citizens, the hukou system and global linkages. Dynamic changes in these components and their interactions drive the urbanisation process in China. The paper then examines how each of the two tracks of urbanisation contributed to the urbanisation process that occurred in China between 1982 and 2000. Copyright © 2006 John Wiley & Sons, Ltd.
Nanostructure formation in polymer thin films influenced by humidity
Authors: Gliemann Hartmut , Almeida Arlete Tavares , Petri Denise Freitas Siqueira , Schimmel Thomas
Published: October 2006

The influence of relative humidity (RH) during the film preparation on the surface morphology and on the material distribution of the resulting technical polymer blend films consisting of poly (methyl methacrylate) (PMMA) and poly (vinyl butyral) (PVB) is investigated by atomic force microscopy. Both pure polymers and polymer blends with different compositions of PVB/PMMA dissolved in tetrahydrofuran (THF) were used. Polymer films prepared under dry conditions (RH < 20%) are compared with those that have the same polymer composition but were prepared under increased humidity conditions (RH > 80%). The films consisting of the pure polymers showed a nonporous surface morphology for low‐humidity preparation conditions, whereas high‐humidity preparation conditions lead to porous PVB and PMMA films, respectively. These pores are explained as the result of a breath figure formation. In the case of the polymer blend films containing both polymers, porous or phase‐separated surface structures were observed even at low‐humidity conditions. A superposition of the effects of phase separation and breath figure formation is observed in the case of polymer blend films prepared under high‐humidity conditions. Atomic force microscopy (AFM) images taken before and after the treatment with ethanol as a selective solvent for PVB indicate that PMMA is deposited on top of a PVB layer in the case of the low‐humidity preparation process whereas for high‐humidity conditions the silicon substrate is covered with a PMMA film. Copyright © 2006 John Wiley & Sons, Ltd.
An empirical study of Java bytecode programs
Authors: Collberg Christian , Myles Ginger , Stepp Michael
Published: October 2006

We present a study of the static structure of real Java bytecode programs. A total of 1132 Java jar‐files were collected from the Internet and analyzed. In addition to simple counts (number of methods per class, number of bytecode instructions per method, etc.), structural metrics such as the complexity of control‐flow and inheritance graphs were computed. We believe this study will be valuable in the design of future programming languages and virtual machine instruction sets, as well as in the efficient implementation of compilers and other language processors. Copyright © 2006 John Wiley & Sons, Ltd.
Intrapartum translabial ultrasound (ITU): sonographic landmarks and correlation with successful vacuum extraction
Authors: Henrich W. , Dudenhausen J. , Fuchs I. , Kämena A. , Tutschek B.
Published: October 2006

Objective

Having studied intrapartum translabial ultrasound (ITU) to define easily obtainable sonographic criteria during maternal pushing, we used it dynamically immediately before vacuum extraction to determine its use in predicting successful operative vaginal delivery.

Methods

In a pilot study, maternal and fetal landmarks were determined sonographically during maternal pushing from a mid‐sagittal translabial insonation using a curved array transducer in women delivering singleton fetuses in cephalic presentation spontaneously. With this transducer placed infrapubically (‘infrapubic plane’), easily obtainable landmarks and signs were: (i) the ‘infrapubic line’, perpendicular to the long axis of the pubic joint and extending dorsally from its inferior margin in a mid‐sagittal plane, (ii) the widest fetal head diameter and its movement with regard to the infrapubic line during pushing, and (iii) the ‘head direction’ with respect to the long axis of the symphysis. A three‐dimensional reconstruction from a computed tomographic (CT) dataset of a normal female pelvis was then used to quantify accurately the spatial relationship between the infrapubic line and the anatomical landmarks. Finally, 20 pregnant women in spontaneous term labor with normal singleton fetuses in cephalic presentation and clinical indication for vacuum extraction were studied by ITU immediately before operative vaginal delivery.

Results

CT reconstruction demonstrated the infrapubic line to be 3 cm cranial to the parallel interspinous plane. Eleven of the 20 vacuum deliveries with the ‘head‐up’ sign (head pointing ventrally) and objective descent of the fetal head below the infrapubic line, both noted at the height of pushing, resulted in successful (‘simple’ or ‘moderately difficult’) operative delivery. Lack of descent or lack of passage below the infrapubic line and horizontal or downward head direction were poor prognostic signs.

Conclusions

ITU provides objective information on the dynamics of the second stage of labor, head station and head direction. ITU may be used to assess the prognosis for operative vaginal delivery. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.
Minimizing the effect of deafness and hidden terminal problem in wireless ad hoc networks using directional antennas
Authors: Gossain Hrishikesh , Cordeiro Carlos , Agrawal Dharma P.
Published: October 2006

In this work we address the issue of deafness and hidden terminal problem in mobile ad hoc networks (MANETs) using directional antennas. To minimize these effects, we propose a MAC protocol for directional Antennas (MDA) which employs a novel enhanced directional network allocation vector (EDNAV) scheme and an efficient technique of diametrically opposite directions (DOD) transmission of RTS and CTS packets. We compare MDA with IEEE 802.11 and two recently proposed directional MAC (DMAC) schemes and results show that MDA outperforms these protocols in the majority of scenarios investigated. We also point out that the performance does depend on the network topology and the traffic pattern.

A shorter version of this has appeared in Globecom 2005.

Copyright © 2006 John Wiley & Sons, Ltd.
Variant maple syrup urine disease (MSUD)—The entire spectrum
Authors: Simon E. , Flaschker N. , Schadewaldt P. , Langenbeck U. , Wendel U.
Published: October 2006

Background: In the rare inborn autosomal recessive disorder maple syrup urine disease (MSUD) the accumulation of the branched‐chain amino acids (BCAAs) and their metabolic products results in acute and chronic brain dysfunction. About 20% of the patients suffer from non‐classic variant forms of MSUD of different clinical severity. Aim: Up to now variant cases have mostly been published as individual case reports; the aim of this study was to give a comparative description of 16 individuals (aged 6–30 years) with different forms of variant MSUD. Methods: Laboratory data, information on clinical course and treatment as well as aspects of developmental, intellectual and social outcome were obtained retrospectively. Data from in vitro and in vivo methods measuring the degree of enzyme deficiency were included. Results: In addition to a mild phenotype, which fits well into the so‐called intermittent variant, and a more severe phenotype with a wider range from a mild variant to an almost classic form, which fits well into the so‐called intermediate variant, we assume the existence of an asymptomatic, non‐disease variant of MSUD. These clinical phenotypes are not unambiguously differentiable on the basis of biochemical parameters. Conclusion: A continuum of clinical severity from asymptomatic to very severe (border to classic) exists in variant MSUD. Apart from newborns with classic MSUD, also those with variant forms benefit from early diagnosis and start of adequate treatment.
Outcome Following Conservative Treatment of Metacarpophalangeal Collateral Ligament Avulsion Fractures of the Finger
Authors: SAWANT N. , KULIKOV Y. , GIDDINS G. E. B.
Published: October 2006

Avulsion fractures of the metacarpophalangeal joints are uncommon and there are few reports on their outcome after conservative treatment. We treated seven such patients with fracture fragment sizes between 10% and 25% of the width of the articular surface on the radiograph by early active mobilisation in neighbour strapping. The outcome of treatment was assessed at a mean follow-up of 57 (range 8–94) months. The mean visual analogue pain score was 0.6 (range 0–2) and the mean visual analogue function score was 9 out of 10 (range 6–10). The mean DASH score was 3.1 (range 0–12.5). All but one patient had normal grip strength and a full range of finger movement. We believe that the majority of avulsion fractures of the metacarpophalangeal joint can be managed successfully without surgery.
Evaluation of quality of life and psychiatric morbidity in patients with malignant tumours of the skull base
Authors: Martinez-Devesa P , Barnes M L , Alcock C J , Kerr R S C , Milford C A
Published: October 2006

In general, patients with malignant tumours of the skull base have a poor prognosis. Treatment may have a disfiguring physical and disabling mental effect on patients.

To evaluate the effect of treatment on physical and mental quality of life in patients with skull base malignancy, we conducted a cross-sectional patient survey of 18 patients treated for such tumours, using the University of Washington (version 4) quality of life questionnaire and the hospital anxiety and depression scale.

The total quality of life score (median value) was 980 (550–1125). Patients with anterior skull base malignancy scored lower than those with lateral skull base malignancy (p=0.003).

In general, the worst individual domain scores were: mood (64 per cent); activity (69 per cent); and, specifically for patients with anterior skull base malignancy, taste (54 per cent, p=0.004) and anxiety (60 per cent, p=0.034).

One-third of skull base cancer patients were at risk of suffering from mental distress and psychiatric morbidity (indicated as a score of more than seven on the hospital anxiety and depression scale).
A long term follow up of conchal flap meatoplasty in chronic otitis externa
Authors: Kumar P Jayanth , Smelt G J C
Published: October 2006

A long-standing diffuse chronic otitis externa can lead to itching. Resultant scratching may then lead to irreversible skin changes with canal stenosis by scar tissue. The poor ventilation and increased humidity gives rise to bacterial and fungal growths leading to breakdown of the skin defences and worsening itching. This vicious itching–scratch cycle or downward spiral often fails to respond to medical treatment. For these cases a simple conchal flap meatoplasty may improve ventilation of the external auditory canal and may lead to a self cleaning ear. We reviewed 84 patients who had undergone conchal flap meatoplasty in Calderdale and Huddersfield NHS Trust Hospitals from April 1993 to June 2002. A long-term follow up of conchal flap meatoplasty in chronic otitis externa showed no records of complications or further otitis in 93.2 per cent of cases. Thus surgical intervention plays an important role in the treatment of otitis externa not responding to treatment.
Should FDG-PET scanning be routinely used for patients with an unknown head and neck squamous primary?
Authors: Silva P , Hulse P , Sykes A J , Carrington B , Julyan P J , Homer J J , Hastings D L , Slevin N J
Published: October 2006

Background: Between 1 and 2 per cent of head and neck squamous cell carcinoma patients will reveal no evidence of a primary malignancy. The management of this group poses many problems, including the morbidity associated with wide field irradiation as well as the difficulty in treatment when a primary does emerge. The aim of this study was to assess the use of fluoro-deoxy-glucose positron emission tomography (FDG-PET) imaging in patients presenting with an unknown head and neck primary and to consider its routine use in such patients.

Methods: We enrolled 25 patients into our study over a four year period. They all presented with a histologically proven, metastatic, squamous cell carcinoma of the neck for which no primary could be found despite full clinical, endoscopic and radiological evaluation with computed tomography (CT) and/or magnetic resonance imaging (MRI). Additionally, all the patients underwent imaging using FDG-PET. The images were interpreted by two radiologists experienced in PET imaging.

Results: A primary was identified in nine of the 25 patients (42 per cent); however, of these patients, six had false positive results and only three patients were true positives with supportive histology. In the remaining 16 patients, no abnormality was identified on CT, MRI or PET. Of these 16 patients, two eventually displayed a primary carcinoma, the other 14 patients remaining without evidence of any primary.

Conclusion: Despite the high number of positive PET scans, the actual true positive rate was 3/9 (33 per cent); conversely, the true negative rate was 14/16 (88 per cent). We conclude from this study that there is a role for FDG-PET in the patient with an unknown head and neck primary, particularly in the context of a negative PET scan.
Granular cell tumour arising from the Kiesselbach's area of the nasal septum
Authors: Sasaki T , Yamamoto K , Akashi T
Published: October 2006

An extremely rare case of a granular cell tumour arising from the right Kiesselbach's area (Little's area) of the nasal septum is reported. A 69-year-old Japanese woman consulted our clinic and her chief complaints were of continuous serous discharge, stuffiness and occasional slight bleeding from the right nasal cavity. Fibrescopy showed a multilocular mass, which was provisionally considered a nasal polyp. Surgical excision was attempted. During surgery, the tumour shrank markedly following local application of adrenaline, suggestive of hypervascularity. The tumour was successfully excised by careful dissection after cauterisation of the mucosa surrounding the tumour. Histopathological examination revealed morphological features of granular cell tumour immunopositive for S-100 protein. This is the first report of granular cell tumour arising from the Kiesselbach's area in the English literature. The eccentric behaviour of the tumour and the management of a granular cell tumour arising from this area are discussed, together with a literature review.
Cerebellar vermis lesions and tumours of the fourth ventricle in patients with positional and positioning vertigo and nystagmus
Authors: Shoman N , Longridge N
Published: October 2006

Positional and positioning vertigo and nystagmus syndromes are usually due to peripheral vestibular dysfunction. The most common form is benign paroxysmal positioning. In this paper, we discuss more serious aetiologies in the differential diagnosis for patients presenting with a history suggestive of benign paroxysmal positioning vertigo. We draw attention to the diagnosis of cerebellar vermis lesions and tumours of the fourth ventricle by presenting two cases of patients with positional nystagmus of so called benign paroxysmal type. We review the literature on positional nystagmus, highlighting key findings on history and physical examination to aid in the correct diagnosis of benign paroxysmal positioning vertigo, and to differentiate it from the rare yet sinister central aetiologies that can present with positional vertigo of the benign positional type. This is with the aim to avoid over-investigating a common presentation without missing a serious diagnosis.
Family cluster of cholesteatoma
Authors: Homøe P , Rosborg J
Published: October 2006

Objective: We report an extremely rare case of family clustering of cholesteatoma.

Method: Case reports and a review of the world literature concerning cholesteatoma and heredity are presented.

Results: The family consists of parents and seven siblings of whom the mother and three sons have been surgically treated for cholesteatoma. All cholesteatomas in the family are acquired and all have a history of otitis media. Cholesteatomas occur with an incidence of 5/100 000 in Greenland, corresponding to two to three new cholesteatoma patients per year among the 57 000 inhabitants of Greenland. The family is very exceptional and interesting for further research concerning heredity in the pathogenesis of acquired cholesteatoma.

Conclusion: To our knowledge this is the first report in the world literature of family clustering of acquired cholesteatoma. This case indicates that hereditary factors interplay with other factors in the pathogenesis of cholesteatoma.
Superior semicircular canal dehiscence with a large tegmental defect
Authors: Mahendran S , Sunkaraneni V S , Baguley D M , Axon P R
Published: October 2006

We report on the presentation and clinical manifestations of superior semicircular canal dehiscence in association with a large defect of the tegmen tympani in a 41-year-old woman with no previous history of trauma. Based on this case we recommend that clinicians consider the possibility of superior semicircular canal dehiscence in patients presenting with symptoms associated with tegmen defects.
Cracking Down on the Cunhamenas: Renegade Amazonian Traders under Pombaline Reform
Authors: SOMMER BARBARA A.
Published: October 2006

The 1750 Treaty of Madrid prompted Portuguese civil and ecclesiastical authorities under Sebastião José de Carvalho e Melo (later the Marquis of Pombal) to strengthen crown control of the Brazilian Amazon. Pombal's brother, Francisco Xavier de Mendonça Furtado, governor and captain-general of the State of Grão-Pará and Maranhão, and Bishop Fr. Miguel de Bulhões e Sousa sought to supplant the missionaries, especially the Jesuits, and rein in autonomous backwoods Indian traders, called cunhamenas (Tupi for male in-law). The Lisbon Inquisition collaborated by prosecuting the infamous mameluco Pedro de Braga, a powerful interethnic intermediary on the Rio Negro, who was condemned for practicing indigenous rites and accepting multiple wives from tribal chiefs.
New findings about the influence of smoke from fires on the cloud‐to‐ground lightning characteristics in the Amazon region
Authors: Fernandes Widinei A. , Pinto Iara R. C. A. , Pinto Osmar , Longo Karla M. , Freitas Saulo R.
Published: October 2006

In the last decade many authors have found evidence on the influence of smoke from fires on the cloud‐to‐ground (CG) lightning characteristics, both in the lifetime scale of individual storms and on a climatological scale. In general, the observations indicate that the peak current and percentage of positive flashes increase in thunderstorms injected with smoke, while the negative peak current decreases. This article investigates the validity of these findings in thunderstorms injected with large concentrations of smoke from fires in the Amazon region, comparing CG lightning characteristics in the dry (polluted) and wet (clean) seasons, as well as using a new methodology, based on results of a numerical simulation model of atmospheric transport of tracers coupled to a biomass burning emission model. The results confirm the previous findings and, in addition, give a first estimation of the sensitivity of these parameters to changes in the smoke concentration.
Surface changes in solar irradiance due to aerosols over central Himalayas
Authors: Dumka U. C. , Satheesh S. K. , Pant P. , Hegde P. , Krishna Moorthy K.
Published: October 2006

During a comprehensive aerosol field campaign as a part of the ISRO‐GBP, extensive measurements of radiative fluxes at the surface were made during December 2004 at Manora Peak, in the Shivalik ranges of the Central Himalayas. The surface radiative fluxes were used to estimate aerosol radiative forcing. Our analysis clearly shows that during the clean atmospheric conditions over Manora Peak, the observed aerosol radiative forcing is in good agreement to those of modeled ones, while for the higher aerosol optical depths (AODs), modeled values are significantly smaller than the observed ones. It was observed that at Manora Peak, the anthropogenic aerosols (from valley below) transported upwards by evolution of boundary layer during the daytime provide an atmosphere conducive for ‘mixed’ aerosols. Focused efforts are needed to address this issue for which simultaneous observations at high altitude site with those in nearby valley are essential.
Evaluation of mortality trajectories in evolutionary biodemography
Authors: Munch Stephan B. , Mangel Marc
Published: October 2006

An important task in evolutionary biodemography is to determine the schedule of survival and reproduction as the outcome of natural selection acting on life histories. We do this by using a model in which the state of the organism is characterized by mass and accumulated damage, both of which are affected by activity and which affect the rate of mortality. Focusing on growth during the juvenile period, we determine the level of activity that maximizes reproductive value. Given this, we are able to project forward and determine the trajectory of mortality for an individual following the optimal life history, given the physiological and reproductive parameters. We show that there are two main classes of juvenile mortality trajectories: U-shaped (such as recently reported for prereproductive humans) and steadily declining and we are able to connect the shape of the mortality trajectory with the physiological and reproductive parameters characterizing the life history. Our work shows the importance of state in models of evolutionary biodemography and the power of modern computational methods to illuminate biological process.
Anisotropic mechanosensing by mesenchymal stem cells
Authors: Kurpinski Kyle , Chu Julia , Hashi Craig , Li Song
Published: October 2006

Mesenchymal stem cells (MSCs) are a potential source for the construction of tissue-engineered vascular grafts. However, how vascular mechanical forces regulate the genetic reprogramming in MSCs is not well understood. Mechanical strain in the vascular wall is anisotropic and mainly in the circumferential direction. We have shown that cyclic uniaxial strain on elastic substrates causes the cells to align perpendicularly to the strain axis, which is different from that in the vascular wall. To simulate the vascular cell alignment and investigate the anisotropic mechanical sensing by MSCs, we used soft lithography to create elastomeric membranes with parallel microgrooves. This topographic pattern kept MSCs aligned parallel to the strain axis, and the cells were subjected to 5% cyclic uniaxial strain (1 Hz) for 2–4 days. DNA microarray analysis revealed global gene expression changes, including an increase in the smooth muscle marker calponin 1, decreases in cartilage matrix markers, and alterations in cell signaling (e.g., down-regulation of the Jagged1 signaling pathway). In addition, uniaxial strain increased MSC proliferation. However, when micropatterning was used to align cells perpendicularly to the axis of mechanical strain, the changes of some genes were diminished, and MSC proliferation was not affected. This study suggests that mechanical strain plays an important role in MSC differentiation and proliferation, and that the effects of mechanotransduction depend on the orientation of cells with respect to the strain axis. The differential cellular responses to the anisotropic mechanical environment have important implications in cardiovascular development, tissue remodeling, and tissue engineering.
Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium
Authors: Zhou Jilin , Jang Young Pyo , Kim So Ra , Sparrow Janet R.
Published: October 2006

Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). Several lines of investigation also indicate that bis-retinoid pigments, such as A2E, that accumulate as lipofuscin in retinal pigment epithelial (RPE) cells, contribute to the disease process. In an investigation of a potential trigger for complement activation in AMD, we explored the notion that the complex mixture of products resulting from photooxidation of A2E might include a range of fragments that could be recognized by the complement system as “foreign” and that could serve to activate the complement system, leading to low-grade inflammation. To this end, we established an
in vitro
assay by using human serum as a source of complement, and we measured products of C3 activation by enzyme immunoassay. Accordingly, we found that the C3 split products inactivated C3b (iC3b) and C3a were elevated in serum, overlying ARPE-19 cells that had accumulated A2E and were irradiated to induce A2E photooxidation. Precoating of microtiter plates with two species of oxidized A2E, peroxy-A2E, and furano-A2E, followed by incubation with serum, also activated complement. We suggest that products of the photooxidation of bis-retinoid lipofuscin pigments in RPE cells could serve as a trigger for the complement system, a trigger than would predispose the macula to disease and that, over time, could contribute to chronic inflammation. These findings link four factors that have been posited as being associated with AMD: inflammation, oxidative damage, drusen, and RPE lipofuscin.
Evolution of complexity in signaling pathways
Authors: Soyer Orkun S. , Bonhoeffer Sebastian
Published: October 2006

It is not clear how biological pathways evolve to mediate a certain physiological response and why they show a level of complexity that is generally above the minimum required to achieve such a response. One possibility is that pathway complexity increases due to the nature of evolutionary mechanisms. Here, we analyze this possibility by using mathematical models of biological pathways and evolutionary simulations. Starting with a population of small pathways of three proteins, we let the population evolve with mutations that affect pathway structure through duplication or deletion of existing proteins, deletion or creation of interactions among them, or addition of new proteins. Our simulations show that such mutational events, coupled with a selective pressure, leads to growth of pathways. These results indicate that pathways could be driven toward complexity via simple evolutionary mechanisms and that complexity can arise without any specific selective pressure for it. Furthermore, we find that the level of complexity that pathways evolve toward depends on the selection criteria. In general, we find that final pathway size tends to be lower when pathways evolve under stringent selection criteria. This leads to the counterintuitive conclusion that simple response requirements on a pathway would facilitate its evolution toward higher complexity.
The pathogen-associated
iroA
gene cluster mediates bacterial evasion of lipocalin 2
Authors: Fischbach Michael A. , Lin Hening , Zhou Lu , Yu Yang , Abergel Rebecca J. , Liu David R. , Raymond Kenneth N. , Wanner Barry L. , Strong Roland K. , Walsh Christopher T. , Aderem Alan , Smith Kelly D.
Published: October 2006

Numerous bacteria cope with the scarcity of iron in their microenvironment by synthesizing small iron-scavenging molecules known as siderophores. Mammals have evolved countermeasures to block siderophore-mediated iron acquisition as part of their innate immune response. Secreted lipocalin 2 (Lcn2) sequesters the
Escherichia coli
siderophore enterobactin (Ent), preventing
E. coli
from acquiring iron and protecting mammals from infection by
E. coli
. Here, we show that the
iroA
gene cluster, found in many pathogenic strains of Gram-negative enteric bacteria, including
E. coli
,
Salmonella
spp., and
Klebsiella pneumoniae
, allows bacteria to evade sequestration of Ent by Lcn2. We demonstrate that C-glucosylated derivatives of Ent produced by
iroA
-encoded enzymes do not bind purified Lcn2, and an
iroA
-harboring strain of
E. coli
is insensitive to the growth inhibitory effects of Lcn2
in vitro
. Furthermore, we show that mice rapidly succumb to infection by an
iroA
-harboring strain of
E. coli
but not its wild-type counterpart, and that this increased virulence depends on evasion of host Lcn2. Our findings indicate that the
iroA
gene cluster allows bacteria to evade this component of the innate immune system, rejuvenating their Ent-mediated iron-acquisition pathway and playing an important role in their virulence.
Role of histone tails in chromatin folding revealed by a mesoscopic oligonucleosome model
Authors: Arya Gaurav , Schlick Tamar
Published: October 2006

The role of each histone tail in regulating chromatin structure is elucidated by using a coarse-grained model of an oligonucleosome incorporating flexible histone tails that reproduces the conformational and dynamical properties of chromatin. Specifically, a tailored configurational-bias Monte Carlo method that efficiently samples the possible conformational states of oligonucleosomes yields positional distributions of histone tails around nucleosomes and illuminates the nature of tail/core/DNA interactions at various salt milieus. Analyses indicate that the H4 histone tails are most important in terms of mediating internucleosomal interactions, especially in highly compact chromatin with linker histones, followed by H3, H2A, and H2B tails in decreasing order of importance. In addition to mediating internucleosomal interactions, the H3 histone tails crucially screen the electrostatic repulsion between the entering/exiting DNA linkers. The H2A and H2B tails distribute themselves along the periphery of chromatin fibers and are important for mediating fiber/fiber interactions. A delicate balance between tail-mediated internucleosomal attraction and repulsion among linker DNAs allows the entering/exiting linker DNAs to align perpendicular to each other in linker-histone deficient chromatin, leading to the formation of an irregular zigzag-folded fiber with dominant pair-wise interactions between nucleosomes
i
and
i
± 4.
Liquid–crystalline aqueous clay suspensions
Authors: Michot Laurent J. , Bihannic Isabelle , Maddi Solange , Funari Sérgio S. , Baravian Christophe , Levitz Pierre , Davidson Patrick
Published: October 2006

This article demonstrates the occurrence of a true isotropic/nematic transition in colloidal Brownian aqueous suspensions of natural nontronite clay. The liquid–crystalline character is further evidenced by polarized light microscopy and small-angle x-ray scattering experiments in the presence and absence of modest external magnetic fields. The complete phase diagram ionic strength/volume fraction then exhibits a clear biphasic domain in the sol region just before the gel transition in contrast with the situation observed for other swelling clays in which the sol/gel transition hinders the isotropic/nematic transition. Small-angle x-ray scattering measurements of gel samples reveal strong positional and orientational orders of the particles, proving unambiguously the nematic character of the gel and, thus, clearly refuting the still prevalent “house of cards” model, which explains the gel structure by means of attractive interactions between clay platelets. Such order also is observed in various other swelling clay minerals; therefore, this very general behavior must be taken into account to reach a better understanding of the rheological properties and phase behavior of these systems.
Induction and repair of zinc-finger nuclease-targeted double-strand breaks in
Caenorhabditis elegans
somatic cells
Authors: Morton Jason , Davis M. Wayne , Jorgensen Erik M. , Carroll Dana
Published: October 2006

Zinc-finger nucleases are chimeric proteins consisting of engineered zinc-finger DNA-binding motifs attached to an endonuclease domain. These proteins can induce site-specific DNA double-strand breaks in genomic DNA, which are then substrates for cellular repair mechanisms. Here, we demonstrate that engineered zinc-finger nucleases function effectively in somatic cells of the nematode
Caenorhabditis elegans
. Although gene-conversion events were indistinguishable from uncut DNA in our assay, nonhomologous end joining resulted in mutations at the target site. A synthetic target on an extrachromosomal array was targeted with a previously characterized nuclease, and an endogenous genomic sequence was targeted with a pair of specifically designed nucleases. In both cases, ≈20% of the target sites were mutated after induction of the corresponding nucleases. Alterations in the extrachromosomal targets were largely products of end-filling and blunt ligation. By contrast, alterations in the chromosomal target were mostly deletions. We interpret these differences to reflect the abundance of homologous templates present in the extrachromosomal arrays versus the paucity of such templates for repair of chromosomal breaks. In addition, we find evidence for the involvement of error-prone DNA synthesis in both homologous and nonhomologous pathways of repair. DNA ligase IV is required for efficient end joining, particularly of blunt ends. In its absence, a secondary end-joining pathway relies more heavily on microhomologies in producing deletions.
Rel/NF-κB double mutants reveal that cellular immunity is central to
Drosophila
host defense
Authors: Matova Nina , Anderson Kathryn V.
Published: October 2006

Studies on
Drosophila
immunity have focused on the humoral response, whereas less is known about the
Drosophila
cellular immunity. Here we show that mutants that lack the
Drosophila
Rel/NF-κB proteins Dorsal and Dif have very few blood cells, are constitutively infected by opportunistic microbes, and die from infection as larvae. When the double mutants are grown in microbe-free conditions, the animals are rescued from chronic infection and many survive to adult stages. Thus, Dif and Dorsal are required for survival because they protect the animal from infection by microbes from the environment. Specific expression of
Dif
or
dorsal
in the blood cell lineage is sufficient to restore blood cell number, clear microbes, and allow survival to the adult stage. These findings demonstrate that the cellular immune response is essential for the ability of
Drosophila
to survive in their standard laboratory environment, and that Dif and Dorsal control crucial aspects of the cellular immune response, including blood cell survival and the ability to fight off microbial infection.
The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis
Authors: Yang Gong , Rosen Daniel G. , Zhang Zhihong , Bast Robert C. , Mills Gordon B. , Colacino Justin A. , Mercado-Uribe Imelda , Liu Jinsong
Published: October 2006

Epithelial–stromal interactions play a critical role in tumor initiation and progression; cancer-associated stroma, but not normal stroma, is known to be tumor-promoting. However, the molecular signal used by epithelial cancer cells to reprogram normal stroma to a tumorigenic stroma is not known. Here, we present evidence to suggest that the chemokine growth-regulated oncogene 1 (Gro-1) may be one such signaling molecule. We showed that the expression of Gro-1 is activated by RAS and is vital for cell survival and the malignant transformation of ovarian epithelial cells. Surprisingly, we found that Gro-1 is a potent inducer of senescence in stromal fibroblasts and that this effect depends on functional p53. Senescent fibroblasts induced by Gro-1 can promote tumor growth whereas abrogation of senescence through immortalization results in loss of such tumor promoting activity. We also demonstrated that stromal fibroblasts adjacent to epithelial cancer cells are senescent in human ovarian cancer specimens and in heterografts from RAS-transformed human ovarian epithelial cells and ovarian cancer cells. Moreover, Gro-1 was expressed at significantly higher amounts in ovarian cancer than in normal tissues and was higher in serum samples from women with ovarian cancer than in serum from women without ovarian cancer. These findings provide strong evidence that RAS-induced Gro-1 can reprogram the stromal microenvironment through the induction of senescence of fibroblasts and thus can promote tumorigenesis. Therefore, Gro-1 may be a therapeutic target as well as a diagnostic marker in ovarian cancer.
Identification of a histidine-tyrosine cross-link in the active site of the
cbb
3
-type cytochrome
c
oxidase from
Rhodobacter sphaeroides
Authors: Rauhamäki Virve , Baumann Marc , Soliymani Rabah , Puustinen Anne , Wikström Mårten
Published: October 2006

The heme-copper oxidases constitute a superfamily of terminal dioxygen-reducing enzymes located in the inner mitochondrial or in the bacterial cell membrane. The presence of a mechanistically important covalent bond between a histidine ligand of the copper ion (Cu
B
) in the active site and a generally conserved tyrosine residue nearby has been shown to exist in the canonical cytochrome
c
oxidases. However, according to sequence alignment studies, this critical tyrosine is missing from the subfamily of

cbb
3

-type oxidases found in certain bacteria. Recently, homology modeling has suggested that a tyrosine residue located in a different helix might fulfill this role in these enzymes. Here, we show directly by methods of protein chemistry and mass spectrometry that there is indeed a covalent link between this tyrosine and the copper-ligating histidine. The identity of the cross-linked tyrosine was determined by showing that the cross-link is not formed when this residue is replaced by phenylalanine, even though structural integrity is maintained. These results suggest a universal functional importance of the histidine-tyrosine cross-link in the mechanism of O
2
reduction by all heme-copper oxidases.
Folding of the C-terminal bacterial binding domain in statherin upon adsorption onto hydroxyapatite crystals
Authors: Goobes Gil , Goobes Rivka , Schueler-Furman Ora , Baker David , Stayton Patrick S. , Drobny Gary P.
Published: October 2006

Statherin is an enamel pellicle protein that inhibits hydroxyapatite (HAP) nucleation and growth, lubricates the enamel surface, and is recognized by oral bacteria in periodontal diseases. We report here from solid-state NMR measurements that the protein's C-terminal region folds into an α-helix upon adsorption to HAP crystals. This region contains the binding sites for bacterial fimbriae that mediate bacterial cell adhesion to the surface of the tooth. The helical segment is shown through long-range distance measurements to fold back onto the intermediate region (residues Y16–P28) defining the global fold of the protein. Statherin, previously shown to be unstructured in solution, undergoes conformation selection on its substrate mineral surface. This surface-induced folding of statherin can be related to its functionality in inhibiting HAP crystal growth and can explain how oral pathogens selectively recognize HAP-bound statherin.
Definition of the mitochondrial proteome by measurement of molecular masses of membrane proteins
Authors: Carroll Joe , Fearnley Ian M. , Walker John E.
Published: October 2006

The covalent structure of a protein is incompletely defined by its gene sequence, and mass spectrometric analysis of the intact protein is needed to detect the presence of any posttranslational modifications. Because most membrane proteins are purified in detergents that are incompatible with mass spectrometric ionization techniques, this essential measurement has not been made on many hydrophobic proteins, and so proteomic data are incomplete. We have extracted membrane proteins from bovine mitochondria and detergent-purified NADH:ubiquinone oxidoreductase (complex I) with organic solvents, fractionated the mixtures by hydrophilic interaction chromatography, and measured the molecular masses of the intact membrane proteins, including those of six subunits of complex I that are encoded in mitochondrial DNA. These measurements resolve long-standing uncertainties about the interpretation of the mitochondrial genome, and they contribute significantly to the definition of the covalent composition of complex I.