bluuebunny/crossref_metadata_2025 huggingface dataset:
Effetcs of ontogenetic scaling on resource exploitation and cohort size distributions
Authors: Huss Magnus , Byström Pär , Persson Lennart
Published: October 2009

Variation in growth rates among individuals leading to the formation of broad size distributions is commonly observed in animal cohorts. Here we use laboratory derived size–scaling relationships to identify mechanisms driving changes in size distribution patterns within cohorts during early ontogeny. We introduced young‐of‐the‐year perchPerca fluviatiliscohorts with different variation in body size distributions in pond enclosures. We kept the exploitative competitive environment constant by adjusting the number of introduced fish such that metabolic requirements were constant between different treatments. Based on modelling results we theoretically derived relative growth rates of differently sized fish when only taken exploitative competitive interactions into account. In agreement with predictions we found that initial variation in body size was negatively correlated with subsequent changes in body size variation in the pond experiment. Corresponding results were obtained in a field study covering 13 studied young‐of‐the‐year perch cohorts in a small lake. Besides having a lower maximum growth capacity, initially large fish also suffered more from resource limitation in our experiment. The results suggest that exploitation competition is a major factor behind growth patterns in young fish cohorts, generally leading to size convergence. To explain the commonly observed pattern of size divergence in animal cohorts, including fish, we suggest that differential timing of diet shifts or mechanisms not related to exploitative interactions must be taken into account. For diet shifts to lead to size divergence we suggest that individuals with an initial size advantage need access to an exclusive prey which has a high growth potential. This, in turn, allows initially larger individuals to surf on a wave of growing prey while individuals only capable to feed on a depressed initial resource experience low growth rates.
Lag‐phases in alien plant invasions: separating the facts from the artefacts
Authors: Aikio Sami , Duncan Richard P. , Hulme Philip E.
Published: October 2009

Temporal trends in biological invasions are often described by a lag‐phase of little or no increase in species occurrence followed by an increase‐phase in which species occurrence rises rapidly. While several biological and environmental mechanisms may underlie lag‐phases, they may also represent statistical artefacts or temporal changes in sampling effort. To date, distinguishing the facts from these artefacts has not been possible. Here we describe a method for estimating the lag‐phase in cumulative records of species occurrence, using a piecewise regression model that explicitly differentiates the lag and increase phases. We used the von Bertalanffy, logistic, linear and exponential functions to model the increase phase, and identified the best‐fitting function using model selection techniques. We confirmed the accuracy of our method using simulated data and then estimated the length of the lag‐phase (tlag), the maximum collection rate (r) and the projected asymptotic number of records (K) using herbarium records for 105 weed species in New Zealand, while accounting for changes in sampling effort. Nearly all the New Zealand weed species had a lag‐phase, which averaged around 20–30 years, with 4% of species having a lag‐phase greater than 40 years. In more than two thirds of the cases, the accumulation of records was best modelled with the decelerating von Bertalanffy function, despite the tendency for temporal variation in sampling effort to force cumulative herbarium records to follow the sigmoidal shape of a logistic curve. A positive correlation between r and K is consistent with the assumption that the final distribution of an alien plant species reflects its rate of spread. Seemingly rare but fast‐spreading aliens may thus become tomorrow's noxious weeds. A positive correlation between inflection year and r warns that the weeds that have only begun to spread relatively recently may spread faster than previously known invaders.
Long‐Term Results of Endosteal Implants Following Radical Oral Cancer Surgery with and without Adjuvant Radiation Therapy
Authors: Linsen Sabine S. , Martini Markus , Stark Helmut
Published: October 2009

Purpose: The aim of this study was to analyze the long‐term survival of implants and implant‐retained prostheses in patients after ablative surgery of oral cancer with or without adjunctive radiation therapy.

Materials and Methods: Between 1997 and 2008, 66 patients who had undergone ablative tumor surgery in the oral cavity were treated with dental implants (n = 262). Thirty‐four patients received radiation therapy in daily fractions of 2 Gy administered on 18 to 30 days. Implants were inserted in the maxilla (49; 18.7%) or mandible (213; 81.3%), in non‐irradiated residual (65; 24.8%) or grafted bone (44; 16.8%) and in irradiated residual (15.6%) or grafted bone (39; 14.9%). Seventeen fixed protheses and 53 removable dentures (34 bar attachments, 9 telescopic and 10 ball retained dentures) were inserted.

Results: Mean follow‐up after implant insertion was 47.99 (±34.31) months (range 12–140 months). The overall 1‐, 5‐, and 10‐year survival rates of all implants were 96.6%, 96.6%, and 86.9%, respectively. Fourteen implants were lost in nine patients (5.3% of all implants); eight implants were primary losses, and five secondary losses because of an operation of tumor recurrence. There was no significantly lower implant survival for implants inserted into irradiated bone (p = .302), bone and/or soft‐tissue grafts (p = .436), and maxilla or mandible (p = .563). All prosthetic restorations in patients without tumor recurrence could be maintained during the observation period.

Conclusions: Implant survival is not significantly influenced by radiation therapy, grafts (bone and/or soft tissue), or location (maxilla or mandible). However, implants placed in irradiated bone exhibit a higher failure rate during the healing period than those placed in non‐irradiated bone. No superstructure was particularly favorable. Osseointegrated implants can be used successfully in patients with prior history of ablative surgery with and without additional radiation therapy.
A Clinical and Histological Case Series Study on Calcium Sulfate for Maxillary Sinus Floor Augmentation and Delayed Placement of Dental Implants
Authors: Dasmah Amir , Hallman Mats , Sennerby Lars , Rasmusson Lars
Published: October 2009

Background: Maxillary sinus floor augmentation is a procedure that is indicated in cases when the volume of the posterior maxillary bone is inadequate. The goal of this treatment is to obtain sufficient amount of bone tissue in order to gain osseointegration of endosseous implants.

Purpose: The purpose of this study was to conduct a clinical and histological analysis of calcium sulfate (CaS) as bone graft substitute in sinus floor augmentation.

Material and Methods: Ten patients with edentulous maxillas were included in this study. They had moderate to severe atrophy of the posterior maxilla. Surgiplaster (Classimplant®, Rome, Italy) was used as graft material in the maxillary sinus and was covered by BioGide® (Geistlish Pharmaceutical, Wolhusen, Switzerland). After 4 months of graft healing, 40 dental implants were placed and a biopsy for histomorphometry was taken at these occasions. The specimens were viewed by light microscope, and the extent of bone regeneration and remaining graft material was evaluated. Radiographs were taken at the time of sinus augmentation and after 4 months of graft healing.

Results: At the time of abutment surgery, one implant was considered as a failure and was consequently removed, giving a survival rate of 97.5% after 1 year of loading. Radiographs showed a mean of 26.5% shrinkage of the augmented area. A significant resorption of CaS was noted with a mean value of 8.8% of remaining graft material after 4 months of healing. The biopsies also revealed new bone formation with a mean value of 21.2% of the total biopsy area. Histology showed signs of an acellular substitution of CaS with bone‐like tissue.

Conclusion: The results of this study show that new bone regeneration occurs in the maxillary sinus after augmentation with CaS. This enabled successful placement, integration, and loading of dental implants in the posterior maxilla, as only 1 of 40 implants was lost during 1 year of follow‐up.
Factors Affecting Survival and Usefulness of Implants Placed in Vascularized Free Composite Grafts Used in Post–Head and Neck Cancer Reconstruction
Authors: Fenlon Michael R. , Lyons Andrew , Farrell Suzanne , Bavisha Kalpesh , Banerjee Avijit , Palmer Richard M.
Published: October 2009

Background: Bone‐containing vascularized grafts have been used successfully to reconstruct post‐cancer surgical defects. Dental implants can be placed in these bone‐containing grafts to allow implant‐supported prosthodontic reconstruction of these patients.

Purpose: The aim of this study was to evaluate the survival of dental implants used in the rehabilitation of subjects treated with bone‐containing vascularized grafts to compare usability of implants placed at the time of reconstruction and after healing.

Materials and Methods: A cross‐sectional study was undertaken to examine survival rates of implants placed in vascularized bone‐containing grafts either immediately at the time of surgical reconstruction or after 3 months healing. Other factors such as graft type, whether radiation therapy was given, and implant type were recorded.

Results: A total of 41 patients had 145 implants placed in 47 vascularized bone‐containing flaps. Increased failure rate of implants was seen in immediately placed implants. There was also a significant increase in the number of osseointegrated implants that were prosthodontically unusable or sub‐optimally placed in the immediate placement group. Radiation therapy was associated with a significant increase in failure rate. Modern implant surfaces appeared to perform better than machined/turned surfaces. Graft donor site did not influence implant survival.

Conclusion: This study demonstrated the difficulties encountered with immediate placement of dental implants at the time of post‐cancer reconstructive surgery.
Confucian Capitalism and the Paradox of Closure and Structural Holes in East Asian Firms
Authors: Chai Sun-Ki , Rhee Mooweon
Published: October 2009

A long-standing debate has taken place in the organizational sociology and social network literatures about the relative advantages of network closure versus structural holes in the generation of social capital. There is recent evidence that these advantages differ across cultures and between East Asia and the West in particular, but existing network models are unable to explain why or address cultural variation in general. This paper seeks to provide a solution by integrating a culture-embedded rational model of action into the social network model of structure, using this not only to re-examine the closure versus structural hole debate, but also to tie it to the literature on Confucian capitalism and the ‘East Asian Model’ of the firm. We argue that this integrated approach allows us to systematically analyse the relationship between culture and behaviour in networks and, more specifically, to explain why closure has been a more powerful source of productivity in East Asia than the West.
A New Agenda for Research on the Trajectory of Chinese Capitalism
Authors: Fligstein Neil , Zhang Jianjun
Published: October 2009

This article sets a new agenda for research on the trajectory of Chinese capitalism. We first critically review the conflicting views on the causes of China's economic development. Then we suggest that insights from the comparative capitalism and economic sociology literatures can provide theoretical tools to understand the critical features of Chinese capitalism in a more systematic manner. The comparative capitalism literature can help us understand how Chinese capitalism resembles or differs from other varieties of capitalism in terms of the relationships between government, firms, and workers. The literature on economic sociology provides insights about how particular markets have evolved and become stabilized. We use these perspectives to suggest a set of possible research agendas for studying Chinese capitalism.
Global Dickens
Authors: Jordan John O.
Published: October 2009

Intended as a case study in the globalization of literary studies and as part of an effort to help launch the Global Circulation Project under the auspices ofLiterature Compass, the present essay takes the writings of Charles Dickens as its focus. The essay has three primary goals. First, it recounts the story of Professor Ada B. Nisbet’s attempt between the mid‐1960s and 1984 to compile and publish an international bibliography of Dickens, one that would examine and analyze the circulation of Dickens’s writings not only within Anglo‐American literary culture but also in the rest of the world. The essay traces the history of this ambitious project, analyzes the reasons it was never completed, and describes the archive that Professor Nisbet left behind. Second, the essay provides a report, necessarily incomplete, of work published since 1984 and work‐in‐progress that deals with the global circulation of Dickens’s writings. Finally, “Global Dickens” issues an invitation to scholars from around the world to contribute to an ongoing dialogue about the reception and significance of Dickens outside Britain, Europe, and North America.
ERK and cell death: Mechanisms of ERK‐induced cell death – apoptosis, autophagy and senescence
Authors: Cagnol Sebastien , Chambard Jean‐Claude
Published: October 2009

The Ras/Raf/extracellular signal‐regulated kinase (ERK) signaling pathway plays a crucial role in almost all cell functions and therefore requires exquisite control of its spatiotemporal activity. Depending on the cell type and stimulus, ERK activity will mediate different antiproliferative events, such as apoptosis, autophagy and senescence in vitro and in vivo. ERK activity can promote either intrinsic or extrinsic apoptotic pathways by induction of mitochondrial cytochrome c release or caspase‐8 activation, permanent cell cycle arrest or autophagic vacuolization. These unusual effects require sustained ERK activity in specific subcellular compartments and could depend on the presence of reactive oxygen species. We will summarize the mechanisms involved in Ras/Raf/ERK antiproliferative functions.
ERK and cell death: ERK1/2 in neuronal death
Authors: Subramaniam Srinivasa , Unsicker Klaus
Published: October 2009

Extracellular signal‐regulated kinase (ERK) is a versatile protein kinase that regulates many cellular functions. Growing evidence suggests that ERK1/2 plays a crucial role in promoting cell death in a variety of neuronal systems, including neurodegenerative diseases. It is believed that the magnitude and the duration of ERK1/2 activity determine its cellular function. In this review, we summarize recent evidence for a role of ERK1/2 in neuronal death. Furthermore, we discuss the mechanisms involved in ERK1/2 mediating neuronal death.
ERK and cell death: ERK location and T cell selection
Authors: Teixeiro Emma , Daniels Mark A.
Published: October 2009

The selection of functional T cells is mediated by interactions between the T cell antigen receptor and self‐peptide major histocompatibility complex expressed on thymic epithelium. These interactions either lead to survival and development or death. The T cell antigen receptor is an unusual receptor able to signal multiple cell fates. The precise mechanism by which this is achieved has been an area of intense research effort over the years. One model proposes that the differential activation of mitogen‐activated protein kinase pathways contributes to this decision. Here, the role of extracellular signal‐regulated kinase in promoting or preventing apoptosis during thymic selection is discussed.
ERK and cell death: cadmium toxicity, sustained ERK activation and cell death
Authors: Martin Patrick , Pognonec Philippe
Published: October 2009

Extracellular signal‐related kinase (ERK) is a key player in cell signaling. After 25 years of investigation, ERK has been associated with every major aspect of cell physiology. Cell proliferation, cell transformation, protection against apoptosis, among others, are influenced by ERK function. Surprisingly, ERK has also been associated with two apparently opposing processes. The involvement of ERK in cell proliferation has been extensively described, as well as its function in postmitotic cells undergoing differentiation. The analysis of these apparent discrepancies has led to a more precise understanding of the multiple functions and regulations of ERK. More recently, several groups have identified a new and unexpected role for ERK. Although being accepted as an important player in the protection against cell death by apoptosis, it is now clear that ERK can also be directly linked to cell death signaling. Here, we review the role of ERK in cell response to cadmium and its association with cell toxicity. In this system, ERK is subjected to a continuous activation that can last for days, which ultimately results in cell death. Cadmium entry into cells is responsible for this sustained ERK activation, probably via reactive oxygen species production, and protein kinase C has a negative action on this cadmium‐dependent ERK activation by modulating cadmium entry into cells.
The crystal structure of human α‐amino‐β‐carboxymuconate‐ε‐semialdehyde decarboxylase in complex with 1,3‐dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis
Authors: Garavaglia Silvia , Perozzi Silvia , Galeazzi Luca , Raffaelli Nadia , Rizzi Menico
Published: October 2009

The enzyme α‐amino‐β‐carboxymuconate‐ε‐semialdehyde decarboxylase (ACMSD) is a zinc‐dependent amidohydrolase that participates in picolinic acid (PA), quinolinic acid (QA) and NAD homeostasis. Indeed, the enzyme stands at a branch point of the tryptophan to NAD pathway, and determines the final fate of the amino acid, i.e. transformation into PA, complete oxidation through the citric acid cycle, or conversion into NAD through QA synthesis. Both PA and QA are key players in a number of physiological and pathological conditions, mainly affecting the central nervous system. As their relative concentrations must be tightly controlled, modulation of ACMSD activity appears to be a promising prospect for the treatment of neurological disorders, including cerebral malaria. Here we report the 2.0 Å resolution crystal structure of human ACMSD in complex with the glycolytic intermediate 1,3‐dihydroxyacetonephosphate (DHAP), refined to an R‐factor of 0.19. DHAP, which we discovered to be a potent enzyme inhibitor, resides in the ligand binding pocket with its phosphate moiety contacting the catalytically essential zinc ion through mediation of a solvent molecule. Arg47, Asp291 and Trp191 appear to be the key residues for DHAP recognition in human ACMSD. Ligand binding induces a significant conformational change affecting a strictly conserved Trp–Met couple, and we propose that these residues are involved in controlling ligand admission into ACMSD. Our data may be used for the design of inhibitors with potential medical interest, and suggest a regulatory link between de novo NAD biosynthesis and glycolysis.
Arabidopsis thaliana BTB/ POZ‐MATH proteins interact with members of the ERF/AP2 transcription factor family
Authors: Weber Henriette , Hellmann Hanjo
Published: October 2009

In Arabidopsis thaliana, the BTB/POZ‐MATH (BPM) proteins comprise a small family of six members. They have been described previously to use their broad complex, tram track, bric‐a‐brac/POX virus and zinc finger (BTB/POZ) domain to assemble with CUL3a and CUL3b and potentially to serve as substrate adaptors to cullin‐based E3‐ligases in plants. In this article, we show that BPMs can also assemble with members of the ethylene response factor/Apetala2 transcription factor family, and that this is mediated by their meprin and TRAF (tumor necrosis factor receptor‐associated factor) homology (MATH) domain. In addition, we provide a detailed description of BPM gene expression patterns in different tissues and on abiotic stress treatments, as well as their subcellular localization. This work connects, for the first time, BPM proteins with ethylene response factor/Apetala2 family members, which is likely to represent a novel regulatory mechanism of transcriptional control.

Structured digital abstract

 MINT‐7262792: BPM1 (uniprotkb:Q8L765) physically interacts (MI:0915) with RAP2‐4 (uniprotkb:Q8H1E4) by two hybrid (MI:0018)

 MINT‐7262805: BPM1 (uniprotkb:Q8L765) physically interacts (MI:0915) with RAP2‐13 (uniprotkb:Q9LM15) by two hybrid (MI:0018)

 MINT‐7262749: BPM3 (uniprotkb:Q2V416) physically interacts (MI:0915) with RAP2‐4 (uniprotkb:Q8H1E4) by two hybrid (MI:0018)

 MINT‐7262764: BPM3 (uniprotkb:Q2V416) physically interacts (MI:0915) with RAP2‐13 (uniprotkb:Q9LM15) by two hybrid (MI:0018)

 MINT‐7262838, MINT‐7262882, MINT‐7262898, MINT‐7263072: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to BPM1 (uniprotkb:Q8L765) by pull down (MI:0096)

 MINT‐7262911: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to BPM2 (uniprotkb:Q9M8J9) by pull down (MI:0096)

 MINT‐7262935: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to BPM3 (uniprotkb:Q2V416) by pull down (MI:0096)

 MINT‐7262945: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to BPM4 (uniprotkb:Q9SRV1) by pull down (MI:0096)

 MINT‐7262970: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to BPM5 (uniprotkb:Q1EBV6) by pull down (MI:0096)

 MINT‐7262992: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to BPM6 (uniprotkb:A1L4W5) by pull down (MI:0096)

 MINT‐7263095: RAP2‐4 (uniprotkb:Q8H1E4) binds (MI:0407) to RAP2‐4 (uniprotkb:Q8H1E4) by pull down (MI:0096)

 MINT‐7262855: RAP2‐13 (uniprotkb:Q9LM15) binds (MI:0407) to BPM1 (uniprotkb:Q8L765) by pull down (MI:0096)

 MINT‐7263015: BPM1 (uniprotkb:Q8L765) binds (MI:0407) to At4g13620 (uniprotkb:Q9SVQ0) by pull down (MI:0096)

 MINT‐7263047: BPM1 (uniprotkb:Q8L765) binds (MI:0407) to At4g39780 (uniprotkb:O65665) by pull down (MI:0096)
Cholesterol oxidase: biotechnological applications
Authors: Pollegioni Loredano , Piubelli Luciano , Molla Gianluca
Published: October 2009

Cholesterol oxidase is a bacterial FAD‐containing flavooxidase that catalyzes the first reaction in cholesterol catabolism. Indeed, this enzyme catalyzes two reactions: the oxidation of the C3‐OH group of cholesterol (and other sterols) to give cholest‐5‐en‐3‐one; and its isomerization to cholest‐4‐en‐3‐one. In the past several years, the structural and functional characterization of cholesterol oxidase has been developed together with its application as a biological tool. Cholesterol oxidase has been used in biocatalysis for the production of a number of steroids, as an insecticidal protein against boll weevil larvae and, in particular, as a diagnostic enzyme for determining serum levels of cholesterol. These applications prompted various laboratories worldwide to isolate this flavooxidase from different sources and to improve its properties by protein engineering, further increasing our knowledge on its structure–function relationships. These studies also discovered new physiological roles for cholesterol oxidase (e.g. in virulence and as an antifungal sensor). We assume that the investigations of cholesterol oxidase and its applications will continue to grow quickly in the near future, in particular to uncover unexpected, new areas of application.
The N‐terminus of mature human frataxin is intrinsically unfolded
Authors: Prischi Filippo , Giannini Clelia , Adinolfi Salvatore , Pastore Annalisa
Published: October 2009

Frataxin is a highly conserved nuclear‐encoded mitochondrial protein whose deficiency is the primary cause of Friedreich’s ataxia, an autosomal recessive neurodegenerative disease. The frataxin structure comprises a well‐characterized globular domain that is present in all species and is preceded in eukaryotes by a non‐conserved N‐terminal tail that contains the mitochondrial import signal. Little is known about the structure and dynamic properties of the N‐terminal tail. Here, we show that this region is flexible and intrinsically unfolded in human frataxin. It does not alter the iron‐binding or self‐aggregation properties of the globular domain. It is therefore very unlikely that this region could be important for the conserved functions of the protein.
Space, time and nitric oxide – neuronal nitric oxide synthase generates signal pulses
Authors: Salerno John C. , Ghosh Dipak K.
Published: October 2009

The temporal aspects of signaling are critical to the function of signals in communications, feedback regulation and control. The production and transduction of biological signals by enzymes comprises an area of central importance and rapid progress in the biomedical sciences. Treatment of signaling enzymes almost universally employs steady‐state analyses that are suitable for mass catalysis but inappropriate for components in an information channel or a feedback/control system. In the present study, we show that, at 37 °C, neuronal nitric oxide synthase (EC 1.14.13.39) is progressively inhibited by the formation of an inhibited state during the first few turnovers (approximately 200 ms) after the initiation of catalysis, leading to pulse formation of nitric oxide. The general mechanism may be of wide importance in biological signaling.
Assembly of nuclear DNA‐encoded subunits into mitochondrial complex IV, and their preferential integration into supercomplex forms in patient mitochondria
Authors: Lazarou Michael , Smith Stacey M. , Thorburn David R. , Ryan Michael T. , McKenzie Matthew
Published: October 2009

Complex IV is the terminal enzyme of the mitochondrial respiratory chain. In humans, biogenesis of complex IV involves the coordinated assembly of 13 subunits encoded by both mitochondrial and nuclear genomes. The early stages of complex IV assembly involving mitochondrial DNA‐encoded subunits CO1 and CO2 have been well studied. However, the latter stages, during which many of the nuclear DNA‐encoded subunits are incorporated, are less well understood. Using in vitro import and assembly assays, we found that subunits Cox6a, Cox6b and Cox7a assembled into pre‐existing complex IV, while Cox4‐1 and Cox6c subunits assembled into subcomplexes that may represent rate‐limiting intermediates. We also found that Cox6a and Cox7a are incorporated into a novel intermediate complex of approximately 250 kDa, and that transition of subunits from this complex to the mature holoenzyme had stalled in the mitochondria of patients with isolated complex IV deficiency. A number of complex IV subunits were also found to integrate into supercomplexes containing combinations of complex I, dimeric complex III and complex IV. Subunit assembly into these supercomplexes was also observed in mitochondria of patients in whom monomeric complex IV was selectively reduced. We conclude that newly imported nuclear DNA‐encoded subunits can integrate into the complex IV holoenzyme and supercomplex forms by associating with pre‐existing subunits and intermediate assembly complexes.
NF‐κB regulates the transcription of protein tyrosine kinase Tec
Authors: Yu Liang , Simonson Oscar E. , Mohamed Abdalla J. , Smith C. I. Edvard
Published: October 2009

The tyrosine kinase expressed in hepatocellular carcinoma (Tec) is a non‐receptor protein tyrosine kinase (PTK) that is expressed in hematopoietic cells, such as B and T lymphocytes, myeloid lineage cells and neutrophils. Mutations in the human Btk gene cause X‐linked agammaglobulinemia (XLA), but the corresponding mutation in mice results in a much milder defect. However, the combined inactivation of Btk and Tec genes in mice cause a severe phenotype resembling XLA. Tec is involved in the regulation of both B and T lymphocytes, fine‐tuning of TCR/BCR signaling, and also activation of the nuclear factor of activated T cells. Previous work has shown that the transcription factors Sp1 and PU.1 can bind and regulate the Tec promoter. In this study, we demonstrate that NF‐κB is an essential transcription factor for optimal expression of the Tec gene, and identify a unique functionally active NF‐κB binding site in its promoter. The NF‐κB subunit p65/RelA directly induced transcriptional activity of the Tec promoter. Moreover, we also found that proteasome inhibitors, including Bortezomib, repress Tec transcription through inactivation of the NF‐κB signaling pathway. This study, together with our previous findings on the transcriptional regulation of Btk (Bruton’s tyrosine kinase) by proteasome inhibitors, provides important insight into the molecular mechanism(s) underlying the role of NF‐κB in Tec family kinase signaling and lymphocyte development.
UDP‐galactose 4‐epimerase from Kluyveromyces  fragilis – catalytic sites of the homodimeric enzyme are functional and regulated
Authors: Brahma Amrita , Banerjee Nupur , Bhattacharyya Debasish
Published: October 2009

UDP‐galactose 4‐epimerase from Kluyveromyces fragilis is a homodimer containing one catalytic site and one NAD+ as cofactor per subunit. One 5′‐UMP, a competitive inhibitor, binds per dimer of epimerase as isolated and causes inactivation. Addition of 0.2 mm inhibitor to the enzyme in vitro leads to three sequential steps: first, the inhibitor binds to the unoccupied site; second, the inhibitor bound ex vivo is displaced allosterically; and finally, both sites are occupied by the inhibitor. These reactions have been monitored by kinetic lag in substrate conversion, coenzyme fluorescence, protection against trypsin digestion, and reductive inhibition. The transition profiles indicate the existence of a stable intermediate with one inhibitor‐binding site remaining unoccupied. Reductive inhibition of this intermediate reduced the activity to 58% ± 2%, with modification of one catalytic site. A change of conformation of the epimerase upon binding with substrate or inhibitor was evident from fluorescence emission spectra. The epimerase demonstrated a biphasic Michaelis–Menten dependency. The epimerase devoid of 5′‐UMP showed a Michaelis–Menten dependency that can be explained by assuming simultaneous operation of two catalytic sites. A monomeric form of the epimerase was devoid of such regulation. The inhibitory profile of 5′‐UMP also suggested negative cooperativity. Incubation of the epimerase with combinations of substrate analogs rendered one of the sites inactive, supporting the presence of two functional and regulated catalytic sites. Dissimilar kinetic patterns of the reconstituted enzyme after treatment with p‐chloromercuribenzoate indicated stability of the dimeric enzyme against fast association–dissociation, which could otherwise generate multiple forms of the enzyme with functional heterogeneity.
Site‐directed enzymatic PEGylation of the human granulocyte colony‐stimulating factor
Authors: Maullu Carlo , Raimondo Domenico , Caboi Francesca , Giorgetti Alejandro , Sergi Mauro , Valentini Maria , Tonon Giancarlo , Tramontano Anna
Published: October 2009

Poly(ethylene glycol) (PEG) is a widely used polymer employed to increase the circulating half‐life of proteins in blood and to decrease their immunogenicity and antigenicity. PEG attaches to free amines, typically at lysine residues or at the N‐terminal amino acid. This lack of selectivity can present problems when a PEGylated protein therapeutic is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic modification of proteins is one route to overcome this limitation. Bacterial transglutaminases are enzyme candidates for site‐specific modification, but they also have rather broad specificity. The need arises to be able to predict a priori potential PEGylation sites on the protein of interest and, especially, to be able to design mutants where unique PEGylation sites can be introduced when needed. We investigated the feasibility of a computational approach to the problem, using human granulocyte colony‐stimulating factor as a test case. The selected protein is therapeutically relevant and represents a challenging problem, as it contains 17 potential PEGylation sites. Our results show that a combination of computational methods allows the identification of the specific glutamines that are substrates for enzymatic PEGylation by a microbial transglutaminase, and that it is possible to rationally modify the protein and introduce PEG moieties at desired sites, thus allowing the selection of regions that are unlikely to interfere with the biological activity of a therapeutic protein.
Functional and small‐angle X‐ray scattering studies of a new stationary phase survival protein E (SurE) from Xylella fastidiosa– evidence of allosteric behaviour
Authors: Saraiva Antonio M. , Reis Marcelo A. , Tada Susely F. , Rosselli‐Murai Luciana K. , Schneider Dilaine R. S. , Pelloso Alexandre C. , Toledo Marcelo A. S. , Giles Carlos , Aparicio Ricardo , de Souza Anete P.
Published: October 2009

The genome data of bacterium Xylella fastidiosa strain 9a5c has identified several orfs related to its phytopathogenic adaptation and survival. Among these genes, the surE codifies a survival protein E (XfSurE) whose function is not so well understood, but functional assays in Escherichia coli revealed nucleotidase and exopolyphosphate activity. In the present study, we report the XfSurE protein overexpression in E. coli and its purification. The overall secondary structure was analyzed by CD. Small‐angle X‐ray scattering and gel filtration techniques demonstrated that the oligomeric state of the protein in solution is a tetramer. In addition, functional kinetics experiments were carried out with several monophosphate nucleoside substrates and revealed a highly positive cooperativity. An allosteric mechanism involving torsion movements in solution is proposed to explain the cooperative behaviour of XfSurE. This is the first characterization of a SurE enzyme from a phytopathogen organism and, to our knowledge, the first solution structure of a SurE protein to be described.

Structured digital abstract

MINT‐7262492: XfSurE (uniprotkb:Q9PF20) and XfSurE (uniprotkb:Q9PF20) bind (MI:0407) by x ray scattering (MI:0826)

MINT‐7262504: XfSurE (uniprotkb:Q9PF20) and XfSurE (uniprotkb:Q9PF20) bind (MI:0407) by molecular sieving (MI:0071)
Differential tissue‐specific distribution of transcripts for the duplicated fatty acid‐binding protein 10 (fabp10) genes in embryos, larvae and adult zebrafish (Danio rerio)
Authors: Venkatachalam Ananda B. , Thisse Christine , Thisse Bernard , Wright Jonathan M.
Published: October 2009

Genomic and cDNA sequences coding for a fatty acid‐binding protein (FABP) in zebrafish were retrieved from DNA sequence databases. The cDNA codes for a protein of 14.7 kDa (pI = 5.94), and the gene consists of four exons, properties characteristic of most vertebrate FABP genes. Phylogenetic analyses using vertebrate FABPs indicated that this protein is most similar to zebrafish Fabp10. Currently, only one fabp10 gene is annotated in the zebrafish genome. In this article, the notations ‘fabp10a’ and ‘fabp10b’ are used to refer to the duplicate copies of fabp10. The zebrafish fabp10a and fabp10b genes were assigned by radiation hybrid mapping to chromosomes 16 and 19, respectively. On the basis of conserved gene synteny with chicken FABP10 on chromosome 23, zebrafish fabp10a and fabp10b are duplicates resulting from a whole‐genome duplication event early in the ray‐finned fish lineage some 230–400 million years ago. Whole‐mount in situ hybridization detected fabp10b transcripts only in the olfactory vesicles of embryos and larvae, whereas fabp10a transcripts have been shown previously to be present only in the liver of embryos and larvae. In adults, RT‐PCR detected fabp10b transcripts in all tissues assayed. By contrast, fabp10a transcripts were detected only in adult liver, intestine and testis. This differential tissue distribution of transcripts for the duplicated fabp10 genes suggests considerable divergence of their cis‐acting regulatory elements since their duplication.
Zinc finger transcription factor ecotropic viral integration site 1 is induced by all‐trans retinoic acid (ATRA) and acts as a dual modulator of the ATRA response
Authors: Bingemann Sonja C. , Konrad Torsten A. , Wieser Rotraud
Published: October 2009

Ecotropic viral integration site 1 (EVI1) plays important roles in leukaemia and development, and its expression is temporally and spatially highly restricted during the latter process. Nevertheless, the only physiological agent that to date has been shown to regulate transcription of this gene in mammalian cells is all‐trans retinoic acid. Here we describe the identification of a retinoic acid response element that was located in the most distal of several alternative first exons of the human EVI1 gene and was constitutively bound by canonical retinoid receptors in NTERA‐2 teratocarcinoma cells. Furthermore, it was the target of negative feedback by EVI1 on the induction of its own promoter by retinoic acid. This process required a previously described transcription repression domain of EVI1. Extending its role as a modulator of the retinoic acid response, EVI1 had the opposite effect on the RARβ retinoic acid response element, whose induction by all‐trans retinoic acid it enhanced through a mechanism that involved almost all of its known functional domains. Augmentation of the retinoic acid response by EVI1 was also observed for the endogenous RARβ gene. Thus, we have established EVI1 as a novel type of modulator of the retinoic acid response, which can both enhance and repress induction by this agent in a promoter‐specific manner.
Physiological functions of hemocytes newly emerged from the cultured hematopoietic organs in the silkworm, Bombyx mori
Authors: Wang Cheng‐Long , Wang Zhi‐Xiang , Kariuki Michael M. , Ling Qing‐Zhi , Kiguchi Kenji , Ling Er‐Jun
Published: October 2009

Abstract  Cellular immunity is a very important part of insect innate immunity. It is not clear if hemocytes entering the hemolymph require a maturation process to become competent. The establishment of a tissue culture system for the insect hematopoietic organs would enable physiological function assays with hemocytes newly emerged from hematopoietic organs. To this end, we established a hematopoietic organ culture system for the purebred silkworm pnd pS and then studied the physiological functions of the newly emerged hemocytes. We found that Grace's medium supplemented with 10% heated silkworm larval plasma was better for culturing the hematopoietic organs of pnd pS. Newly emerged hemocytes phagocytosed propidium iodide‐labeled bacteria and encapsulated the Iml‐2 coated nickel beads as well as pupal tissue debris. This culture system is therefore capable of generating physiologically functional hemocytes. These hemocytes can be used to study the mechanisms of the hemocyte immune response among others.
White grubs, Holotrichia rustica and Holotrichia mucida (Coleoptera: Scarabaeidae) as pests of teak (Tectona grandis L. f.) seedlings
Authors: Kulkarni Nitin , Paunikar Sanjay , Joshi Kailash Chandra , Rogers John
Published: October 2009

Abstract  Field observations were carried out between 2002 and 2005 on bio‐ecology of white grubs infesting teak (Tectona grandis Linn. f.) seedlings at Ramdongari Forest Nursery, Forest Development Corporation of Maharashtra, Nagpur in central India. The study collected the data required for an integrated pest management strategy against the white grubs. The species damaging teak seedlings were Holotrichia rustica (Burmeister) and H. mucida Gyllenhal. The beetles (adults) of both these species began to emerge just after the pre‐monsoon showers and when the relative humidity had risen rapidly over several days, but before the first monsoon rains. While the adults fed and mated on naturally growing bushes of Ziziphus jujuba, Z. mauritiana, Z. xylopyra, Acacia leucophloea and A. catechu immediately after the emergence from the teak beds in the nursery, the immature stages (grubs) of both species fed on roots of the teak seedling, leading to plant death. This is the first report of (i) damage caused to teak seedlings by grubs of H. rustica and H. mucida, and (ii) of Z. jujuba and Z. mauritiana being hosts for the beetles of H. mucida and H. rustica. It is also the first detailed report on the field bio‐ecology of the H. rustica and H. mucida as major pests of teak. White grubs are among the toughest‐to‐manage pests of economic importance and information presented here on the pest incidence and damage of H. rustica and H. mucida is important to researchers and nursery field managers for the management of these pests on teak.
Sustainable Use of Water from Natural and Social Science Perspectives
Authors: Hauhs Michael , Graefe Olivier
Published: October 2009

Several seemingly incompatible meanings of water coexist today and are implicated in the organisation of sustainable water usage by humans. We review the conceptual basis of the dominating natural science approach to water as a finite resource. This physical approach shows limits relevant for the notion of sustainability. Valuation and interpretation of human–water relationships as meaningful, which are still widespread in practice and are studied by humanities, appear as irrational under this approach. The natural science perspective is complemented by a second, novel modelling paradigm which is based on a refined notion of behaviour and has been developed in computer science. No single model is superior along the whole water cycle, but the varying influences of living systems along the cycle may require different model abstractions and concepts. The novel extended modelling approach can be formally used to accommodate hermeneutic approaches to the meaning of water typical of social sciences. It organises a systematic ‘fact‐value‐integration’ rather than the separation typical of natural science. Hence, traditional and modern approaches to the organisation of sustainable water utilisation can be compared from a consistent and systematic conceptual basis linking natural and social sciences.
The Hydrology of Mediterranean Mountain Areas
Authors: Latron J. , Llorens P. , Gallart F.
Published: October 2009

The study of the hydrology of Mediterranean mountain areas is especially important, as Mediterranean regions are characterized by unevenly distributed water resources that mainly depend on runoff generated in mountain areas. The objective of this article is to review some characteristic features of the hydrology of Mediterranean mountain areas, mainly based on results from small research catchments (less than 10 km2) mostly in Europe and in the United States of America. In addition, data obtained over the last 20 years from the Vallcebre research catchments (Eastern Pyrenees, Spain) are used to illustrate some of the characteristic features. Investigations show that the seasonal temperature evolution in Mediterranean regions has a direct effect on evapotranspiration dynamics, which, in combination with the seasonal dynamics of rainfall, cause the succession of wet and dry or very dry periods during the year. This seasonality of the Mediterranean mountain climate has a strong influence on the spatio‐temporal dynamics of both soil moisture and the water table. The succession of dry and wet periods and the characteristic occurrence of wetting‐up transitions between the two increase the complexity of the rainfall–runoff relationship in Mediterranean mountain areas by triggering a different combination of hydrological processes that depend on catchment wetness conditions. Research that is more process‐orientated is needed, using complementary approaches to further update a perceptual model of the hydrological functioning of Mediterranean mountain catchments. Its objective should be to work out more flexible process‐based modeling structures, which include the strong seasonality of Mediterranean catchments’ hydrology.
Thinking Outside the Box: Engaging Critical Geographic Information Systems Theory, Practice and Politics in Human Geography
Authors: Elwood Sarah
Published: October 2009

Over the past decade or more, Geographic Information Systems (GIS) have been re‐imagined and reconfigured through critical GIS research and practice, as scholars and activist have sought new ways of engaging GIS beyond its characterization in the 1990s as a rationalist and rationalizing tool. Where many existing discussions of the contributions of critical GIS have focused on its position and impacts in GIScience, here I review recent work in critical GIS with an eye toward highlighting its contributions and possibilities in critical human geography. This study examines the theorizations, epistemological frameworks, and methodological innovations are enabling human geographers to engage with GIS, cartography, and geovisual methods in their work in creative ways. I begin by unpacking the ‘critical’ in critical GIS, illustrating how it has drawn upon theory and politics from critical theory to offer a series of key reconceptualizations of GIS and its knowledge‐making repertoire. Then, I illustrate the ever‐diversifying ways in which critical GIS theory and practice are being woven into geographers’ research and activism.
Upregulation of Immunoglobulin‐related Genes in Cortical Sections from Multiple Sclerosis Patients
Authors: Torkildsen Øivind , Stansberg Christine , Angelskår Solveig M. , Kooi Evert‐Jan , Geurts Jeroen J.G. , Van Der Valk Paul , Myhr Kjell‐Morten , Steen Vidar M. , Bø Lars
Published: October 2009

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Microarray‐based global gene expression profiling is a promising method, used to study potential genes involved in the pathogenesis of the disease. In the present study, we have examined global gene expression in normal‐appearing gray matter and gray matter lesions from the cortex of MS patients, and compared them with cortical gray matter samples from controls. We observed a massive upregulation of immunoglobulin (Ig)‐related genes in cortical sections of MS patients. Using immunohistochemistry, the activation of Ig genes seems to occur within plasma cells in the meninges. As synthesis of oligoclonal IgGs has been hypothesized to be caused by the activation of Epstein–Barr virus (EBV)‐infected B‐cells, we screened the brain samples for the presence of EBV by real‐time quantitative polymerase chain reaction (qPCR) and immunohistochemistry, but no evidence of active or latent EBV infection was detected. This study demonstrates that genes involved in the synthesis of Igs are upregulated in MS patients and that this activation is caused by a small number of meningeal plasma cells that are not infected by EBV. The findings indicate that the Ig‐producing B‐cells found in the cerebrospinal fluid (CSF) of MS patients could have meningeal origin.
Refractive errors in children and young adults with Down’s syndrome
Authors: Ljubic Antonela , Trajkovski Vladimir
Published: October 2009

Purpose:  Down’s syndrome (DS) is the most common chromosomal anomaly. Numerous ophthalmic features have been reported. The aim of our study was to investigate the incidence of refractive errors in children and young adults with DS in Macedonia.

Methods:  Fifty‐six children and young adults with DS, aged 2–28 years, from Macedonia, underwent slit‐lamp examination, ocular motility and refraction.

Results:  The overall incidence of refractive errors in the Macedonian children and young adults with DS was 96.4%. A total of 17.8% of the subjects had myopia, 23.2% had hypermetropia and 55.3% had astigmatism. Strabismus was seen in 13 (23.2%) of the subjects (nine had esotropia, three had exotropia, one had hypertropia).

Conclusions:  The incidence of refractive errors in Macedonian children and young adults with DS was similar to that in Asian children. Compared with White (Caucasian) and Asian children with DS, Macedonian children and young adults exhibited lower incidences of hypermetropia and myopia, and a higher incidence of astigmatism, in which oblique astigmatism represented the predominant type.