bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal model of self-replicating nanocells: a physically embodied information-free scenario
Authors: Fellermann Harold , Solé Ricard V
Published: May 2007

The building of minimal self-reproducing systems with a physical embodiment (generically called protocells) is a great challenge, with implications for both theory and applied sciences. Although the classical view of a living protocell assumes that it includes information-carrying molecules as an essential ingredient, a dividing cell-like structure can be built from a metabolism–container coupled system only. An example of such a system, modelled with dissipative particle dynamics, is presented here. This article demonstrates how a simple coupling between a precursor molecule and surfactant molecules forming micelles can experience a growth-division cycle in a predictable manner, and analyses the influence of crucial parameters on this replication cycle. Implications of these results for origins of cellular life and living technology are outlined.
Synthetic Turing protocells: vesicle self-reproduction through symmetry-breaking instabilities
Authors: Macía Javier , Solé Ricard V
Published: May 2007

The reproduction of a living cell requires a repeatable set of chemical events to be properly coordinated. Such events define a replication cycle, coupling the growth and shape change of the cell membrane with internal metabolic reactions. Although the logic of such process is determined by potentially simple physico-chemical laws, modelling of a full, self-maintained cell cycle is not trivial. Here we present a novel approach to the problem that makes use of so-called symmetry breaking instabilities as the engine of cell growth and division. It is shown that the process occurs as a consequence of the breaking of spatial symmetry and provides a reliable mechanism of vesicle growth and reproduction. Our model opens the possibility of a synthetic protocell lacking information but displaying self-reproduction under a very simple set of chemical reactions.
Cloning and expression analysis of insulin‐like growth factor I and II in liver and muscle of sea bass (Dicentrarchus labrax, L.) during long‐term fasting and refeeding
Authors: Terova G. , Rimoldi S. , Chini V. , Gornati R. , Bernardini G. , Saroglia M.
Published: May 2007

The exceptionally fast growth that fish experience after periods of fasting has been called ‘compensatory growth’ or ‘catch‐up’ growth. This phenomenon, reported in a wide range of fish species, has been studied in intensive aquaculture as a means of enhancing feed conversion efficiency, but the mechanisms implicated are complex and not yet fully understood. In the present study, the authors describe the cloning and sequencing of the complete coding sequences of sea bass (Dicentrarchus labrax) insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor‐II (IGF‐II), which are potent mitogens known to play important roles in growth and development. Sea bass IGF‐I has an open reading frame (ORF) of 561 bp that encodes a mature protein of 187 amino acids, whereas IGF‐II has an ORF of 648 bp encoding a mature protein of 216 amino acids. At the amino acid level, sea bass IGF‐I shares a 30% similarity with IGF‐II. The authors then report the pattern of IGF‐I and IGF‐II gene expression in liver and myotomal muscle in response to prolonged fasting and refeeding. Nutritional status significantly influenced IGF‐I messenger RNA copy number in both liver and muscle, inducing a down‐regulation during fasting and an up‐regulation during the recovery from fasting. The trend of IGF‐II response was similar, but different feeding regimens did not affect the amounts of transcript as sharply as in IGF‐I. Taken together these data indicate that IGF‐I and IGF‐II participate in promoting sea bass muscle compensatory growth induced by refeeding.
Problems with the application of cladistics to forest fragmentation studies
Authors: Giannini Norberto , Keller Roberto A.
Published: May 2007

© The Willi Hennig Society 2007.
Phylogeny, evolution and systematics of Moehringia (Caryophyllaceae) as inferred from molecular and morphological data: a case of homology reassessment
Authors: Fior Simone , Karis Per Ola
Published: May 2007

The phylogeny of the genus Moehringia (Caryophyllaceae) is investigated by means of analyzing nuclear (ITS) and chloroplast (matK) sequence data in combination with morphological characters. Parsimony and Bayesian methods yield consistent results, and a common phylogenetic signal is shared by the nuclear and chloroplast data. Morphological characters are affected by a high level of homoplasy, but they provide valuable information when analyzed in combination with the molecular data. Moehringia is paraphyletic to Arenaria with the Iberian taxa belonging to Moehringia sect. Pseudomoehringia McNeill more closely related to Arenaria. This cladistic evidence led us to reinterpret the homology of the key character used in most, if not all, floras, to separate Moehringia from Arenaria, i.e., the seed strophiole. Thorough anatomical studies were carried out to elucidate the ontogeny of the strophiole, which proved different in Moehringia s. str. and the Iberian taxa. Within Moehringia s. str., two sister clades are recognized (i.e., Moehringia sect. Moehringia and M. sect. Latifoliae much as recognized by McNeill, whereas representatives of M. sect. Diversifoliae are assigned to either groups), and biogeographical events related to the Würm glaciation are considered to play a fundamental role in the evolution and present distribution of the genus. The variation of the strophiole is regarded as adaptability to ecological conditions and dispersal agents. We also propose two new combinations and two replacement names: Arenaria glochidisperma (J.M. Mont.) Fior et P.O. Karis, comb. nov., Arenaria tejedensis (Willk.) Fior et P.O. Karis, comb. nov., Arenaria suffruticosa Fior et P.O. Karis, nom. nov. for Moehringia intricata Willk., and Arenaria funiculata Fior et P.O. Karis, nom. nov. for Moehringia fontqueri Pau.

© The Willi Hennig Society 2007.
Critical role for D‐type cyclins in cellular transformation induced by E6/E7 of human papillomavirus type 16 and E6/E7/ErbB‐2 cooperation
Authors: Yasmeen Amber , Hosein Abdel N. , Yu Qunyan , Al Moustafa Ala‐Eddin
Published: May 2007

Recently, we reported that E6/E7 of human papillomavirus (HPV) type 16 cooperates with the ErbB‐2 receptor to induce cellular transformation of human normal oral epithelial (NOE) and mouse normal embryonic fibroblast (NEF) cells. Furthermore, we demonstrated that cyclin D1 is essential for this transformation induced by E6/E7 and E6/E7/ErbB‐2 cooperation using cyclin D1 antisense and knockout (D1−/–) cells. To determine the role of all D‐type cyclins (D1, D2 and D3) in E6/E7/ErbB‐2 cooperation, we examined the effects of E6/E7, ErbB‐2 alone and E6/E7/ErbB‐2 together in NEF, NEF‐D1−/–, NEF‐D2−/– and NEF‐D3−/– cells. We confirm that NEF‐E6/E7 and NEF‐E6/E7/ErbB‐2, but not NEF‐ErbB‐2 cells, induce colony formation in soft agar and tumor formation in nude mice. We report that E6/E7, ErbB‐2 and E6/E7/ErbB‐2 together all fail to induce neoplastic transformation of D1−/– and D2−/– cells in vitro and in vivo. In contrast, E6/E7/ErbB‐2 together but neither E6/E7 nor ErbB‐2 alone provoke cellular transformation of D3−/– cells. Nevertheless, D3−/–E6/E7/ErbB‐2 cells resulted in up to a 60 and 50% decrease in colony and tumor formation in soft agar and nude mice, respectively, compared with NEF‐E6/E7/ErbB‐2 cells. Furthermore, using cyclin D2 small interfering RNA we inhibited tumor and colony formation of the human NOE‐E6/E7‐ErbB‐2‐transformed cell line; in contrast, cyclin D3 small interfering RNA repressed approximately 50% of colony and 40% of tumor formation of E6/E7/ErbB‐2 cooperation in this cell line. These data suggest that cyclins D1, D2 and D3 (to a lesser extent) are important downstream mediators of the cellular transformation induced by E6/E7 and E6/E7/ErbB‐2 cooperation in normal cells. Our data imply that anti‐D‐type cyclin therapies are important in the treatment of human cancers expressing high‐risk HPV or HPV/ErbB‐2. (Cancer Sci 2007; 98: 973–977)
Gene–gene and gene–environment interactions between alcohol drinking habit and polymorphisms in alcohol‐metabolizing enzyme genes and the risk of head and neck cancer in Japan
Authors: Hiraki Akio , Matsuo Keitaro , Wakai Kenji , Suzuki Takeshi , Hasegawa Yasuhisa , Tajima Kazuo
Published: May 2007

Alcohol consumption is a strong risk factor for squamous cell carcinoma of the head and neck (SCCHN). The genetic polymorphisms aldehyde dehydrogenase2 (ALDH2) Glu487Lys and alcohol dehydrogenase 2 (ADH2) His47Arg, which have a strong impact on alcohol metabolism, are common in the Japanese population. To clarify the significance of these polymorphisms in SCCHN carcinogenesis, we conducted a matched case‐control study with 239 incident SCCHN subjects and 716 non‐cancer controls. Both ADH2 Arg/Arg and ALDH2 Glu/Lys were found to be independently associated with increased risk, with odds ratios (OR) of 2.67 (95% confidence interval [CI] 1.51–4.57) and 1.66 (95% CI 1.20–2.31), respectively. Further, compared with subjects having both ADH2 His/His and ALDH2 Glu/Glu, the adjusted OR and its 95% CI for those with both ADH2 Arg/Arg and ALDH2 Glu/Lys was 5.00 (2.32–10.71) in all subjects. This combination effect was evident in heavy drinkers (OR 11.3, 95% CI 2.97–43.3) but not in moderate or non‐drinkers. Statistically significant gene–environment interactions between the two polymorphisms and drinking level were seen (ADH2 P = 0.035, ALDH2, P = 0.013). Furthermore, we also found a statistically significant gene–gene interaction between the two polymorphisms (P = 0.042). In conclusion, this case‐control study showed a significantly increased risk of SCCHN in subjects with the ADH2 Arg/Arg and ALDH2 Glu/Lys polymorphisms in a Japanese population. In addition, our results also demonstrated that this risk was associated with significant gene–gene interactions between ADH2 and ALDH2 polymorphisms, as well as gene–environment interactions between these polymorphisms and alcohol drinking. (Cancer Sci 2007; 98: 1087–1091)
Studies of a germinal centre B‐cell expressed gene, GCET2, suggest its role as a membrane associated adapter protein
Authors: Pan Zenggang , Shen Yulei , Ge Baosheng , Du Cheng , McKeithan Timothy , Chan Wing C
Published: May 2007

GCET2 (Germinal centre B‐cell expressed transcript 2; also named HGAL) is a newly cloned gene that has been shown to be a useful marker for germinal centre (GC) B cells and GC B‐cell derived malignancies, including follicular lymphomas and germinal centre B cell‐like diffuse large B‐cell lymphomas (GCB‐DLBCLs), and is a useful prognosticator for DLBCLs. We report here the biochemical and biological properties of GCET2, which may help to determine its role in the GC reaction. GCET2 is constitutively localised in the plasma membrane but is excluded from lipid rafts. GCET2 does not have a transmembrane domain, and its membrane localisation is mediated by myristoylation and palmitoylation. GCET2 has five conserved putative tyrosine phosphorylation sites, and it can be phosphorylated following pervanadate treatment in B cells. By serially mutating the five tyrosines, the third and fourth tyrosines were found to be essential for GCET2 phosphorylation. GCET2 was phosphorylated when co‐transfected into COS7 cells with protein tyrosine kinases (PTKs) LYN, LCK or SYK, and therefore it could be a substrate of these kinases in B cells. The third tyrosine site (107YENV) of GCET2 is a consensus GRB2 binding site, and GCET2 was found to associate with GRB2 through the third tyrosine following phosphorylation. Our data suggests that GCET2 may be an adaptor protein in GC B cells that transduces signals from GC B‐cell membrane to the cytosol via its association with GRB2.
Gene silencing by DNA methylation in haematological malignancies
Authors: Boultwood Jacqueline , Wainscoat James S.
Published: May 2007

The past decade has seen an explosion of interest in the epigenetics of cancer, with an increasing understanding that this form of genomic modification plays a critical role in pathogenesis. The malignant phenotype results from a step‐wise increase of both genetic abnormalities and epigenetic modifications, leading to dysregulation of critical genes controlling cell growth, differentiation and apoptosis. The methylation of CpG islands within gene promoters is a major epigenetic transcriptional control mechanism that is frequently dysregulated in human cancer. This phenomenon (methylation of CpG islands) plays a critical role in the transcriptional silencing of tumour suppressor genes in cancer and has prompted the development and testing of several demethylating agents aimed at reversing this process. Clinical trials using epigenetically targeted therapies have yielded particularly promising results in the myelodysplastic syndromes (MDS), in which tumour suppressor gene silencing by promoter methylation is a frequent event. Several genes and gene pathways disrupted by aberrant CpG island methylation have now been identified in haematological malignancies, the most frequently studied being the cell cycle inhibitors p16 (now termed CDKN2A; mostly methylated in lymphoid malignancy) and p15 (now termed CDKN2B; commonly methylated in lymphoid and myeloid malignancies). This review will discuss the role that aberrant gene silencing by promoter hypermethylation plays in the molecular pathogenesis of haematological malignancies and assess the clinical potential of demethylating agents for the management of patients.
The effect of menopause on bone mineral density and bone‐related biochemical variables in Indonesian women
Authors: Oemardi Maryantoro , Horowitz Michael , Wishart Judith M. , Morris Howard A. , Need Allan G. , O’Loughlin Peter D. , Nordin B. E. Christopher
Published: May 2007

Objective  To determine the effects of menopause on bone‐related variables in Indonesian women and to compare them with corresponding data in Caucasian Australian women.

Design  A study of bone‐related variables in women aged 45–55 years in Jakarta compared with corresponding historical data from Caucasian Australian women.

Measurements  Dietary intakes, bone mineral density (BMD) and calcium‐related variables in blood and urine.

Results  Dietary calcium, phosphorus and protein intakes were significantly lower in the women from Jakarta than in those from Adelaide (all P < 0·001), probably because of lower milk consumption, but energy intake was similar in the two cities. Indonesian women were shorter and lighter than Australian women (P < 0·001) but had a comparable body mass index (BMI). The Indonesians also had a lower spinal BMD than the Australians but this was accounted for by the differences in height and weight between the two populations. The differences in serum and urinary calcium and phosphate and serum alkaline phosphatase across the menopause were comparable in Indonesian and Australian women but creatinine excretion was 25% lower in Jakarta than in Adelaide (P < 0·001) and this was probably sufficient to account for higher ratios of some urinary solutes to urinary creatinine in the Indonesians. Serum 25‐hydroxyvitamin D (25OHD) levels were significantly lower (P < 0·001) and serum PTH levels significantly higher (P = 0·0045) in Jakarta than in Adelaide.

Conclusions  The differences in bone‐related biochemical variables across the menopause were similar in the two populations, but calcium and protein intake and urine creatinine were lower in Indonesian than in Australian women. Serum 25OHD was lower and PTH higher in the Indonesian women, probably because of their darker skin, their practice of avoiding direct sunlight and the heavy atmospheric pollution in Jakarta.
Tag SNP screening of the PDCD1 gene for association with Graves’ disease
Authors: Newby P. R. , Roberts‐Davies E. L. , Brand O. J. , Heward J. M. , Franklyn J. A. , Gough S. C. L. , Simmonds M. J.
Published: May 2007

Objective  The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD‐1 which is involved in providing a negative signal to activated T cells. Large case‐control studies have shown association of PDCD1 with several autoimmune diseases although, to date, no such studies have been performed for Graves’ disease (GD). The objective of our study was to investigate eight tag SNPs representing the majority of common variation in PDCD1 within a well‐characterized large UK Caucasian GD dataset.

Design  A case control association study of eight polymorphisms.

Patients  2671 Graves’ disease patients and 864 controls.

Measurements  Tests for association with disease.

Results  No association with disease was seen for any of the +4163, +5049, +5318, +5640, +5678 and +7078 SNPs genotyped in this study. Association was detected between the +2375 SNP (P = 0·021, OR = 1·14 [95% CI = 1·01–1·29]) and GD and a small protective effect was seen with the +6799 SNP genotypes (P = 0·028, OR = 0·77 [95% CI = 0·58–1·03]).

Conclusions  This study has, for the first time, shown that small effects within PDCD1 may contribute towards the development of GD, supporting the hypothesis that much of the currently unknown genetic contribution to GD could be due to several small genetic effects with ORs  1·2. Replication of this result is now needed to confirm our findings and justify more detailed fine mapping of a primary aetiological variant in this gene region.
Alterations in the biomass‐specific productivity of periphyton assemblages mediated by fish grazing
Authors: ABE SHIN‐ICHIRO , UCHIDA KAZUO , NAGUMO TAMOTSU , TANAKA JIRO
Published: May 2007

1. In an experimental flume, we examined the effects of a biomass reduction and alteration of taxonomic composition, because of grazing by the fish Plecoglossus altivelis, on the net biomass accumulation of periphyton.

2. Grazed and ungrazed assemblages with different biomass and taxonomic composition were first prepared in fish enclosures and exclosures, respectively. These assemblages were then set out in the flume and incubated for 2 days under grazing‐free conditions to examine (i) the relationship between biomass and biomass accumulation rate and (ii) the effect of taxonomic composition on the relationship between these two.

3. The grazed and ungrazed assemblages were dominated by upright filamentous cyanobacteria and diatoms, respectively. The rate of biomass accumulation decreased with increasing periphyton biomass in both the grazed and ungrazed assemblages, and was lower in the grazed than the ungrazed assemblages at any biomass level.

4. The results showed that the reduction in biomass and the alteration of taxonomic composition due to fish grazing have opposite effects on biomass‐specific productivity. Biomass accumulation rate increased in response to biomass reduction, although a shift in dominance from diatoms to upright filamentous cyanobacteria decreased the overall productivity of the periphyton.
The molecular aetiology of haemophilia A in a New Zealand patient group
Authors: LAURIE A. D. , SHEEN C. R. , HANRAHAN V. , SMITH M. P. , GEORGE P. M.
Published: May 2007

Summary.  The genetic basis of haemophilia A (HA) is well‐established, and many haematology services are supported by molecular biology laboratories that offer factor VIII genetic testing for HA patients. This report describes the results from factor VIII gene (F8) analysis of a New Zealand cohort of 45 proband HA patients. We screened all proband HA patients attending local clinics to determine the molecular basis of disease in each case. We also aimed to evaluate the significance of founder effect in this population and to explain an unusual case of HA in a female patient. HA patients were screened for the common F8 gene inversion mutations using previously described PCR‐based techniques, and for single base substitution mutations using denaturing high performance liquid chromatography and DNA sequencing. Analysis of microsatellite markers located within or near F8 was used to determine identity by descent and trace inheritance patterns of disease alleles. X‐chromosome inactivation (XCI) patterns were detected using methylation specific PCR. Pathogenic F8 gene mutations were detected in all 45 HA patients in this cohort and non‐random XCI was confirmed in a female haemophiliac. We report nine novel F8 mutations, including two splicing mutations, a five nucleotide deletion and a large deletion at the 5′ end of the gene. The molecular aetiology of HA was similar to that described in other studies but the distribution of mutations was unusual due to founder effects, with almost a quarter of all probands being descended from just three individuals.
Attitudes and use of rubber dam by Irish general dental practitioners
Authors: Lynch C. D. , McConnell R. J.
Published: May 2007

Aim  To investigate the attitudes towards and use of rubber dam by Irish general dental practitioners.

Methodology  A pre‐piloted questionnaire was distributed amongst a group of 600 dentists randomly selected from the Irish Register of Dentists. Replies from dentists working in specialist practice or the hospital dental service were excluded. Dentists were surveyed in relation to their use of rubber dam during a variety of operative and root canal treatments, as well as their attitudes to the use of rubber dam in dental practice.

Results  A total of 300 replies were considered from a total of 324 that were received. Seventy‐seven per cent of respondents (n = 231) worked in general dental practice and 23% (n = 69) worked in the Irish Health Board/Community Dental Service. Rubber dam was ‘never’ used by 77% of respondents (n = 228) when placing amalgam restorations in posterior teeth, 52% (n = 147) when placing composite restorations in posterior teeth, and 59% (n = 177) when placing composite restorations in anterior teeth. Rubber dam was ‘never’ used by 39% of respondents (n = 114) when performing root canal treatment on anterior teeth; 32% (n = 84) when performing root canal treatment on premolar teeth; and 26% (n = 51) when performing root canal treatment on molar teeth. Fifty‐seven per cent (n = 171) considered rubber dam ‘cumbersome and difficult to apply’, and 41% (n = 123) considered throat pack ‘as good a prevention against inhalation of endodontic instruments as rubber dam’.

Conclusions  Whilst rubber dam is used more frequently for root canal treatment than operative treatment, its use is limited. This presents quality issues, as well as medico‐legal and safety concerns for both the profession and patients.
Radiological assessment of periapical status using the periapical index: comparison of periapical radiography and digital panoramic radiography
Authors: Ridao‐Sacie C. , Segura‐Egea J. J. , Fernández‐Palacín A. , Bullón‐Fernández P. , Ríos‐Santos J. V.
Published: May 2007

Aim  To compare the use of periapical radiographs and digital panoramic images displayed on monitor and glossy paper in the assessment of the periapical status of the teeth using the periapical index (PAI).

Methodology  A total of 86 subjects were examined. All participants underwent a full‐mouth radiographic survey (14 periapical radiographs) and a panoramic radiography. The periapical status, using the PAI score, of all appraised teeth was assessed.

Results  Periapical radiographs allowed the assessment of the periapical status of 87% of teeth using the PAI. On the contrary, digital radiography had a significantly reduced potential to allow assessment of the periapical status (P < 0.01). Only 57.6% and 34.1% of teeth could be appraised using digital panoramic images displayed on monitor and glossy paper respectively (P < 0.01). The total percentage of teeth with periapical pathosis was five fold higher when assessed with digital panoramic images displayed on glossy paper compared with periapical radiographs (P < 0.01).

Conclusions  Teeth were best viewed on periapical radiographs except maxillary second and third molars, which were better viewed in orthopantomograms. Orthopantomograms on screen were scorable more often than when on printed images. Apical periodontitis was scored more often on paper than on screen, and more often on screen than in periapical radiographs.
Are sugars‐free medicines more erosive than sugars‐containing medicines? An in vitro study of paediatric medicines with prolonged oral clearance used regularly and long‐term by children
Authors: MAGUIRE ANNE , BAQIR WASIM , NUNN JUNE HEATHER
Published: May 2007

Objective.  The reduced use of sugars‐containing (SC) liquid medicines has increased the use of other dose forms, potentially resulting in more widespread dental effects, including tooth wear. The aim of this study was to assess the erosive potential of 97 paediatric medicines in vitro.

Methods.  The study took the form of in vitro measurement of endogenous pH and titratable acidity (mmol). Endogenous pH was measured using a pH meter, followed by titration to pH 7.0 with 0.1‐m NaOH.

Results.  Overall, 55 (57%) formulations had an endogenous pH of < 5.5. The mean (± SD) endogenous pH and titratable acidity for 41 SC formulations were 5.26 ± 1.30 and 0.139 ± 0.133 mmol, respectively; for 56 sugars‐free (SF) formulations, these figures were 5.73 ± 1.53 and 0.413 ± 1.50 mmol (P > 0.05). Compared with their SC bioequivalents, eight SF medicines showed no significant differences for pH or titratable acidity, while 15 higher‐strength medicines showed lower pH (P = 0.035) and greater titratable acidity (P = 0.016) than their lower‐strength equivalents. Chewable and dispersible tablets (P < 0.001), gastrointestinal medicines (P = 0.002) and antibiotics (P = 0.007) were significant predictors of higher pH. In contrast, effervescent tablets (P < 0.001), and nutrition and blood preparations (P = 0.021) were significant predictors of higher titratable acidity.

Conclusions.  Paediatric SF medicines were not more erosive than SC medicines in vitro; a more significant predictor of their erosive potential was dose form.
Idiopathic muscle necrosis in the Norway lobster, Nephrops norvegicus (L.): aetiology, pathology and progression to bacteraemia
Authors: Ridgway I D , Stentiford G D , Taylor A C , Atkinson R J A , Birkbeck T H , Neil D M
Published: May 2007

The pathology and progression of idiopathic muscle necrosis (IMN) in Nephrops norvegicus and possible aetiologies have been investigated. Trawl capture, aerial exposure and handling initiate IMN, and the condition can be induced through periods of aerial exposure alone, in the absence of trawling. Within 24–48 h after trawl capture IMN progresses to a multi‐species bacterial septicaemia, with moribund animals exhibiting clinical signs. The aetiology of this condition has been examined using molecular (16S rRNA gene sequencing) and biochemical (standard taxonomic assays, BiologTM) criteria to characterize bacterial isolates from moribund and healthy animals. Histopathology of the IMN phase reveals a loss of sarcomeric structure with necrotic lesions containing pyknotic nuclei, fragments of myofibrils and connective tissue elements. In the bacterial phase there is extensive loss of abdominal muscle structure, and the presence of rod‐shaped Gram‐negative bacteria in the degrading tissues. The results demonstrate that the IMN condition is connected to stressful conditions imposed on N. norvegicus, but involves no pathogenic agents. This is followed by an opportunistic bacterial infection that causes further tissue spoilage. It is believed that the primary cause of both IMN and bacteraemia is imposed stress, but they are expressed in different time courses.
Applied behaviour analysis: does intervention intensity relate to family stressors and maternal well‐being?
Authors: Schwichtenberg A. , Poehlmann J.
Published: May 2007

Background  Interventions based on applied behaviour analysis (ABA) are commonly recommended for children with an autism spectrum disorder (ASD); however, few studies address how this intervention model impacts families. The intense requirements that ABA programmes place on children and families are often cited as a critique of the programme, although little evidence is available to support this claim. Using Pearlin's (1999) stress process model, this study assessed: (1) whether mothers of children participating in a home‐based ABA programme reported elevated depressive symptoms; and (2) whether ABA intensity related to unmet family needs and maternal feelings of depression, personal strain and mastery.

Method  Forty‐one mothers of children diagnosed with an ASD participated in this study by completing questionnaires about their child's ASD behaviours, unmet family needs, and maternal feelings of depression, personal strain and mastery. Additionally, mothers provided information about their child's intervention programme and their own level of involvement in the programme. At the time of data collection, all families had been running a home‐based ABA programme for at least 6 months.

Results  Single‐sample t‐tests and multiple regression analyses were used to test the proposed hypotheses. Mothers of children participating in a home‐based ABA programme reported more depressive symptoms than mothers of children with other developmental disabilities. Comparisons revealed comparable depressive symptoms between the mothers of the present sample and those in other ASD samples. When considering weekly ABA intensity, mothers reported fewer depressive symptoms when their child was older and when their child participated in more ABA therapy hours. Conversely, mothers who were more involved in their child's ABA programme reported more personal strain.

Conclusions  The findings of this study supported the hypothesis that families participating in ABA experienced elevated depressive symptoms, much like any family raising a child with an ASD, suggesting a potential area for family‐level intervention. Additionally, ABA intensity related to maternal depression and personal strain, and therefore deserves continued attention. Future studies should attempt to replicate these findings with a larger and more representative sample and seek to identify mechanisms through which ABA intensity may influence maternal and family well‐being.
Challenging behaviours: prevalence and topographies
Authors: Lowe K. , Allen D. , Jones E. , Brophy S. , Moore K. , James W.
Published: May 2007

Background  Variations in reported prevalence of challenging behaviour indicate the need for further epidemiological research to support accurate planning of future service provision.

Methods  All services providing for people with learning disabilities across seven unitary authorities, with a total population of 1.2 million, were screened to identify people with challenging behaviour. Interviews were conducted with primary carers to gain data on identified individuals' characteristics and support. Measures designed for a similar study conducted in Manchester University were incorporated to allow direct comparison with earlier findings, together with standardized tools to assess adaptive behaviour and social impairment.

Results  In total, 4.5 (2.5–7.5) people per 10 000 population were rated as seriously challenging, representing 10% (5.5–16.8%) of the learning disability population; the most prevalent general form was other difficult/disruptive behaviour, with non‐compliance being the most prevalent topography. The majority showed multiple behaviours and multiple topographies within each general behaviour category. Also identified were substantial numbers of additional people reported as presenting challenging behaviours at lower degrees of severity.

Conclusions  Prevalence rates for seriously challenging behaviours were comparable to those reported in the earlier studies, thus confirming previous findings. The prevalence of less serious challenging behaviour also has major clinical significance and emphasizes the need for enhanced understanding and skills among personnel within primary‐ and secondary‐tier health, education and social care services, and for strengthening the capacity of community teams to provide behavioural expertise.
Lack of conflict during queen production in the social waspVespula maculifrons
Authors: GOODISMAN MICHAEL A. D. , KOVACS JENNIFER L. , HOFFMAN ERIC A.
Published: May 2007

Social insects display extreme cooperative and helping behaviours. However, social insect colonies are also arenas of intense competitive interactions. One particularly important matter over which colony members may compete centres on the development of sexual offspring. Specifically, colony members may engage in selfish behaviours leading to reproductive competition, whereby individuals either strive to develop as sexuals or assist kin so that close relatives emerge as new reproductives. We investigated whether reproductive competition occurred in the polyandrous social waspVespula maculifrons. We genotypedV. maculifronsworkers and new queens at eight polymorphic microsatellite loci to determine if larvae of particular genotypes were reared as gynes more frequently than expected by chance. However, we found no significant evidence of reproductive competition in this species. The proportional contributions of males to workers and new queens did not vary within colonies. Moreover, male reproductive skew did not differ between workers and new queens. Finally, novel statistical techniques uncovered no evidence of patriline reversal, the phenomenon whereby males that contribute little to worker production contribute substantially to new queen production. Consequently, we conclude that individual level selection operating to increase the frequency of selfish behaviours that would lead to reproductive competition has been nullified by colony‐level selection acting to maintain colony efficiency and cooperation.
Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation
Authors: Manetti Andrea G. O. , Zingaretti Chiara , Falugi Fabiana , Capo Sabrina , Bombaci Mauro , Bagnoli Fabio , Gambellini Gabriella , Bensi Giuliano , Mora Marirosa , Edwards Andrew M. , Musser James M. , Graviss Edward A. , Telford John L. , Grandi Guido , Margarit Immaculada
Published: May 2007

Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram‐positive human pathogen responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year. GAS infections require the capacity of the pathogen to adhere to host tissues and assemble in cell aggregates. Furthermore, a role for biofilms in GAS pathogenesis has recently been proposed. Here we investigated the role of GAS pili in biofilm formation. We demonstrated that GAS pilus‐negative mutants, in which the genes encoding either the pilus backbone structural protein or the sortase C1 have been deleted, showed an impaired capacity to attach to a pharyngeal cell line. The same mutants were much less efficient in forming cellular aggregates in liquid culture and microcolonies on human cells. Furthermore, mutant strains were incapable of producing the typical three‐dimensional layer with bacterial microcolonies embedded in a carbohydrate polymeric matrix. Complemented mutants had an adhesion and aggregation phenotype similar to the wild‐type strain. Finally, in vivo expression of pili was indirectly confirmed by demonstrating that most of the sera from human patients affected by GAS‐mediated pharyngitis recognized recombinant pili proteins. These data support the role of pili in GAS adherence and colonization and suggest a general role of pili in all pathogenic streptococci.
Viral nanomotors for packaging of dsDNA and dsRNA
Authors: Guo Peixuan , Lee Tae Jin
Published: May 2007

While capsid proteins are assembled around single‐stranded genomic DNA or RNA in rod‐shaped viruses, the lengthy double‐stranded genome of other viruses is packaged forcefully within a preformed protein shell. This entropically unfavourable DNA or RNA packaging is accomplished by an ATP‐driven viral nanomotor, which is mainly composed of two components, the oligomerized channel and the packaging enzymes. This intriguing DNA or RNA packaging process has provoked interest among virologists, bacteriologists, biochemists, biophysicists, chemists, structural biologists and computational scientists alike, especially those interested in nanotechnology, nanomedicine, AAA+ family proteins, energy conversion, cell membrane transport, DNA or RNA replication and antiviral therapy. This review mainly focuses on the motors of double‐stranded DNA viruses, but double‐stranded RNA viral motors are also discussed due to interesting similarities. The novel and ingenious configuration of these nanomotors has inspired the development of biomimetics for nanodevices. Advances in structural and functional studies have increased our understanding of the molecular basis of biological movement to the point where we can begin thinking about possible applications of the viral DNA packaging motor in nanotechnology and medical applications.
Thiol‐disulphide oxidoreductase modules in the low‐GC Gram‐positive bacteria
Authors: Kouwen Thijs R. H. M. , Van Der Goot Annemieke , Dorenbos Ronald , Winter Theresa , Antelmann Haike , Plaisier Marie‐Claire , Quax Wim J. , Van Dijl January Maarten , Dubois Jean‐Yves F.
Published: May 2007

Disulphide bond formation catalysed by thiol‐disulphide oxidoreductases (TDORs) is a universally conserved mechanism for stabilizing extracytoplasmic proteins. In Escherichia coli, disulphide bond formation requires a concerted action of distinct TDORs in thiol oxidation and subsequent quinone reduction. TDOR function in other bacteria has remained largely unexplored. Here we focus on TDORs of low‐GC Gram‐positive bacteria, in particular DsbA of Staphylococcus aureus and BdbA‐D of Bacillus subtilis. Phylogenetic analyses reveal that the homologues DsbA and BdbD cluster in distinct groups typical for Staphylococcus and Bacillus species respectively. To compare the function of these TDORs, DsbA was produced in various bdb mutants of B. subtilis. Next, we assessed the ability of DsbA to sustain different TDOR‐dependent processes, including heterologous secretion of E. coli PhoA, competence development and bacteriocin (sublancin 168) production. The results show that DsbA can function in all three processes. While BdbD needs a quinone oxidoreductase for activity, DsbA activity appears to depend on redox‐active medium components. Unexpectedly, both quinone oxidoreductases of B. subtilis are sufficient to sustain production of sublancin. Moreover, DsbA can functionally replace these quinone oxidoreductases in sublancin production. Taken together, our unprecedented findings imply that TDOR systems of low‐GC Gram‐positive bacteria have a modular composition.
The global regulator H‐NS binds to two distinct classes of sites within the Tn10 transpososome to promote transposition
Authors: Ward Chris M. , Wardle Simon J. , Singh Randeep K. , Haniford David B.
Published: May 2007

The histone‐like nucleoid structuring protein (H‐NS) is a global transcriptional regulator that influences stress response and virulence pathways in Gram‐negative bacteria. H‐NS also promotes Tn10 transposition by binding directly to the transpososome and inducing a conformational change in the transpososome that favours intermolecular transposition events. H‐NS binds preferentially to curved DNA and can bend non‐curved DNA, it self‐oligomerizes and can interact with other proteins. To determine what functions of H‐NS are important in promoting Tn10 transposition, we have examined the ability of two mutant forms of H‐NS, P116S and 1–64, to act in Tn10 transposition. We provide evidence that the initial interaction of H‐NS with the transpososome is dependent on H‐NS binding to a specific structure in DNA flanking the transposon end. Additional molecules of H‐NS then bind within the transposon end. This latter event appears to be directed by H‐NS binding to the Tn10 transposase protein, and is important in maintaining the transpososome in a conformation that promotes intermolecular transposition. The binding of H‐NS to a transposase protein is a novel function for this important regulatory molecule.
Glycosylphosphatidylinositol (GPI) anchor is required in Aspergillus fumigatus for morphogenesis and virulence
Authors: Li Hong , Zhou Hui , Luo Yuanming , Ouyang Haomiao , Hu Hongyan , Jin Cheng
Published: May 2007

In yeast, glycosylphosphatidylinositol (GPI) is essential for viability and plays an important role in biosynthesis and organization of cell wall. Initiation of the GPI anchor biosynthesis is catalysed by the GPI–N‐acetylglucosaminyltransferase complex (GPI–GnT). The GPI3 (SPT14) gene is thought to encode the catalytic subunit of GPI–GnT complex. In contrast to Saccharomyces cerevisiae, little is known about the GPI biosynthesis in filamentous fungi. In this study, the afpig‐a gene was identified as the homologue of the GPI3/pig‐A gene in Aspergillus fumigatus, an opportunistic fungal pathogen. By replacement of the afpig‐a gene with a pyrG gene, we obtained the null mutants. Although the Δafpig‐a mutant exhibited a significant increased cell lysis instead of temperature‐sensitive or conditional lethal phenotype associated to the GPI3 mutant of yeast, they could survive at temperatures from 30°C to 50°C. The analysis of the mutants showed that a completely blocking of the GPI anchor synthesis in A. fumigatus led to cell wall defect, abnormal hyphal growth, rapid conidial germination and aberrant conidiation. In vivo assays revealed that the mutant exhibited a reduced virulence in immunocompromised mice. The GPI anchor was not essential for viability, but required for the cell wall integrity, morphogenesis and virulence in A. fumigatus.
A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding
Authors: Hartshorne Robert S. , Kern Melanie , Meyer Björn , Clarke Thomas A. , Karas Michael , Richardson David J. , Simon Jörg
Published: May 2007

In bacterial c‐type cytochromes, the haem cofactor is covalently attached via two cysteine residues organized in a haem c‐binding motif. Here, a novel octa‐haem c protein, MccA, is described that contains only seven conventional haem c‐binding motifs (CXXCH), in addition to several single cysteine residues and a conserved CH signature. Mass spectrometric analysis of purified MccA from Wolinella succinogenes suggests that two of the single cysteine residues are actually part of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic characterization of MccA identified an unusual high‐potential haem c with a red‐shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c that exceptionally bind haem via only one thioether bridge. A haem lyase gene was found to be specifically required for the maturation of MccA in W. succinogenes. Equivalent haem lyase‐encoding genes belonging to either the bacterial cytochrome c biogenesis system I or II are present in the vicinity of every known mccA gene suggesting a dedicated cytochrome c maturation pathway. The results necessitate reconsideration of computer‐based prediction of putative haem c‐binding motifs in bacterial proteomes.
Temperature‐induced regulation of RpoS by a small RNA in Borrelia burgdorferi
Authors: Lybecker Meghan C. , Samuels D. Scott
Published: May 2007

The alternative sigma factor RpoS (σ38 or σS) plays a central role in the reciprocal regulation of the virulence‐associated major outer surface proteins OspC and OspA in Borrelia burgdorferi, the Lyme disease spirochete. Temperature is one of the key environmental signals controlling RpoS, but the molecular mechanism by which the signal is transduced remains unknown. Herein, we identify and describe a small non‐coding RNA, DsrABb, that regulates the temperature‐induced increase in RpoS. A novel 5′ end of the rpoS mRNA was identified and DsrABb has the potential to extensively base‐pair with the upstream region of this rpoS transcript. We demonstrate that B. burgdorferi strains lacking DsrABb do not upregulate RpoS and OspC in response to an increase in temperature, but do regulate RpoS and OspC in response to changes in pH and cell density. Analyses of the rpoS and ospC steady‐state mRNA levels in the dsrABb mutant indicate that DsrABb regulates RpoS post‐transcriptionally. The 5′ and 3′ ends of DsrABb were mapped, demonstrating that at least four species exist with sizes ranging from 213 to 352 nucleotides. We hypothesize that DsrABb binds to the upstream region of the rpoS mRNA and stimulates translation by releasing the Shine‐Dalgarno sequence and start site from a stable secondary structure. Therefore, we postulate that DsrABb is a molecular thermometer regulating RpoS in Borrelia burgdorferi.
Transmembrane transport of peptidoglycan precursors across model and bacterial membranes
Authors: Van Dam Vincent , Sijbrandi Robert , Kol Matthijs , Swiezewska Ewa , De Kruijff Ben , Breukink Eefjan
Published: May 2007

Translocation of the peptidoglycan precursor Lipid II across the cytoplasmic membrane is a key step in bacterial cell wall synthesis, but hardly understood. Using NBD‐labelled Lipid II, we showed by fluorescence and TLC assays that Lipid II transport does not occur spontaneously and is not induced by the presence of single spanning helical transmembrane peptides that facilitate transbilayer movement of membrane phospholipids. MurG catalysed synthesis of Lipid II from Lipid I in lipid vesicles also did not result in membrane translocation of Lipid II. These findings demonstrate that a specialized protein machinery is needed for transmembrane movement of Lipid II. In line with this, we could demonstrate Lipid II translocation in isolated Escherichia coli inner membrane vesicles and this transport could be uncoupled from the synthesis of Lipid II at low temperatures. The transport process appeared to be independent from an energy source (ATP or proton motive force). Additionally, our studies indicate that translocation of Lipid II is coupled to transglycosylation activity on the periplasmic side of the inner membrane.
CCD BVI photometry and Coravel observations of stars in the open cluster NGC 2489
Authors: Piatti Andrés E. , Clariá Juan J. , Mermilliod Jean-Claude , Parisi María C. , Ahumada Andrea V.
Published: May 2007

We present CCD BVI photometry for the southern open cluster NGC 2489 and its surrounding field. The sample consists of 2182 stars measured in an area of 13.6 × 13.6 arcmin2, extending down to V∼ 21.5. These data are supplemented with CORAVEL radial-velocity observations for seven red giant candidates. A cluster angular radius of 6.7 ± 0.6 arcmin, equivalent to 3.5 ± 0.3 pc, is estimated from star counts carried out inside and outside the cluster region. The comparison of the cluster colour–magnitude diagrams with isochrones of the Padova group yields E(B−V) = 0.30 ± 0.05, E(V−I) = 0.40 ± 0.05 and V−MV= 12.20 ± 0.25 for log t= 8.70 (t= 500+130−100 Myr) and Z= 0.019. NGC 2489 is then located at 1.8 ± 0.3 kpc from the Sun and 25 pc below the Galactic plane. The analysis of the kinematical data allowed us to confirm cluster membership for six red giants, one of them being a spectroscopic binary. A mean radial velocity of 38.13 ± 0.33 km s−1 was derived for the cluster red giants. The properties of a sample of open clusters aligned along the line of sight of NGC 2489 are examined.