994 resultados para Primary mutation
Resumo:
The aim of the study was to clarify the occurrence, and etiological and prognostic factors of primary fallopian tube carcinoma (PFTC). We studied the sociodemographic determinants of the incidence of PFTC in Finland and the role of chlamydial infections and human papillomavirus infections as risk factors for PFTC. Serum tumor markers were studied as prognostic factors for PFTC. We also evaluated selected reproductive factors (parity, sterilization and hysterectomy) as risk or protective factors of PFTC. The risks of second primary cancers after PFTC were also studied. The age-adjusted incidence of PFTC in Finland increased to 5.4 / 1,000,000 in 1993 97. The incidence rate was higher in the cities, but the relative rise was higher in rural areas. Women in the two highest social classes showed a 1.8 fold incidence compared with those in the lowest. Women in agriculture and those not working outside the home showed only half the PFTC incidence of those in higher socioeconomic occupations. Pretreatment serum concentrations of hCGβ, CA125 and TATI were evaluated as prognostic markers for PFTC. Elevated hCGβ values (above the 75th percentile, 3.5 pmol/L; OR 2.49, 95% CI 1.22 5.09), stage and histology were strong independent prognostic factors for PFTC. The effects of parity, sterilization and hysterectomy on the risk of PFTC were studied in a case control-study with 573 PFTC cases from the Finnish Cancer Registry. In multivariate analysis parity was the only significant protective factor as regards PFTC, with increasing protection associated with increasing number of deliveries. In univariate analysis sterilization gave borderline protection against PFTC and the protective effect increased with time since the operation. In multivariate analysis the protection did not reach statistical significance. Chlamydial and human papillomavirus (HPV) infections were studied in two separate seroepidemiological case-control studies with 78 PFTC patients. The incidence of women with positive HPV or chlamydial serology was the same in PFTC patients and in the control group and was not found to be a risk factor for PFTC. Finally, the possible risk of a second primary cancer after diagnosis and treatment of PFTC in a cohort of 2084 cases from 13 cancer registries followed for second primary cancers within the period 1943 2000 was studied. In PFTC patients, second primary cancers were 36% more common than expected (SIR 1.36, 95% CI 1.13 1.63). In conclusion, the incidence of PFTC has increased in Finland, especially in higher social classes and among those in certain occupations. Elevated serum hCGβ reflect a worsened prognosis. Parity is a clear protective factor, as is previous sterilization. After PFTC there is a risk of second primary cancers, especially colorectal, breast, lung and bladder cancers and non-lymphoid leukemia. The excess of colorectal and breast cancers after PFTC may indicate common effects of earlier treatments, or they could reflect common effects of lifestyle or genetic, immunological or environmental background.
Resumo:
Aims: We report on the outcome of the Exeter Contemporary flanged cemented all-polyethylene acetabular component with a mean follow-up of 12 years (10 to 13.9). This study reviewed 203 hips in 194 patients. 129 hips in 122 patients are still in situ; 66 hips in 64 patients were in patients who died before ten years, and eight hips (eight patients) were revised. Clinical outcome scores were available for 108 hips (104 patients) and radiographs for 103 hips (100 patients). Patients and Methods: A retrospective review was undertaken of a consecutive series of 203 routine primary cemented total hip arthroplasties (THA) in 194 patients. Results: There were no acetabular component revisions for aseptic loosening. Acetabular revision was undertaken in eight hips. In four hips revision was necessitated by periprosthetic femoral fractures, in two hips by recurrent dislocation, in one hip for infection and in one hip for unexplained ongoing pain. Oxford and Harris hip scores demonstrated significant clinical improvement (all p < 0.001). Radiolucent lines were present in 37 (36%) of the 103 acetabular components available for radiological evaluation. In 27 of these, the line was confined to zone 1. No component had migrated. Conclusion: Kaplan–Meier survivorship, with revision for aseptic loosening as the endpoint, was 100% at 12.5 years and for all causes was 97.8% (95% confidence interval 95.6 to 100) when 40 components remained at risk. The Exeter Contemporary flanged cemented acetabular component demonstrates excellent survivorship at 12.5 years. Take home message: The Exeter Contemporary flanged cemented acetabular component has excellent clinical outcomes and survivorship when used with the Exeter stem in total hip arthroplasty.
Resumo:
Background The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. Methods This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. Findings Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months [95% CI 10·6–12·9] with afatinib vs 10·9 months [9·1–11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57–0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9–15·0] with afatinib vs 11·5 months [10·1–13·1] with gefitinib; HR 0·73 [95% CI 0·58–0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. Interpretation Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.
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Background We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. Methods Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. Findings Median follow-up in LUX-Lung 3 was 41 months (IQR 35–44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31–37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28·2 months (95% CI 24·6–33·6) in the afatinib group and 28·2 months (20·7–33·2) in the pemetrexed-cisplatin group (HR 0·88, 95% CI 0·66–1·17, p=0·39). In LUX-Lung 6, median overall survival was 23·1 months (95% CI 20·4–27·3) in the afatinib group and 23·5 months (18·0–25·6) in the gemcitabine-cisplatin group (HR 0·93, 95% CI 0·72–1·22, p=0·61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33·3 months (95% CI 26·8–41·5) in the afatinib group versus 21·1 months (16·3–30·7) in the chemotherapy group (HR 0·54, 95% CI 0·36–0·79, p=0·0015); in LUX-Lung 6, it was 31·4 months (95% CI 24·2–35·3) versus 18·4 months (14·6–25·6), respectively (HR 0·64, 95% CI 0·44–0·94, p=0·023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27·6 months (19·8–41·7) in the afatinib group versus 40·3 months (24·3–not estimable) in the chemotherapy group (HR 1·30, 95% CI 0·80–2·11, p=0·29); in LUX-Lung 6, it was 19·6 months (95% CI 17·0–22·1) versus 24·3 months (19·0–27·0), respectively (HR 1·22, 95% CI 0·81–1·83, p=0·34). In both trials, the most common afatinib-related grade 3–4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3–4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3–4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). Interpretation Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials.
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The incorporation of dUMP during replication or the deamination of cytosine in DNA results in the occurrence of uracils in genomes. To maintain genomic integrity, uracil DNA glycosylases (UDGs) excise uracil from DNA and initiate the base-excision repair pathway. Here, we cloned, purified and biochemically characterized a family 5 UDG, UdgB, from Mycobacterium smegmatis to allow us to use it as a model organism to investigate the physiological significance of the novel enzyme. Studies with knockout strains showed that compared with the wild-type parent, the mutation rate of the udgB(-) strain was approximately twofold higher, whereas the mutation rate of a strain deficient in the family 1 UDG (ung(-)) was found to be similar to 8.4-fold higher. Interestingly, the mutation rate of the double-knockout (ung(-)ludgB(-)) strain was remarkably high, at similar to 19.6-fold. While CG to TA mutations predominated in the ung(-) and ung(-)/udgb(-) strains, AT to GC mutations were enhanced in the udgB(-) strain. The ung(-)/udgB(-) strain was notably more sensitive to acidified nitrite and hydrogen peroxide stresses compared with the single knockouts (ung(-) or udgB(-)). These observations reveal a synergistic effect of UdgB and Ung in DNA repair, and could have implications for the generation of attenuated strains of Mycobacterium tuberculosis.
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Objective: To nationally trial the Primary Care Practice Improvement Tool (PC-PIT), an organisational performance improvement tool previously co-created with Australian primary care practices to increase their focus on relevant quality improvement (QI) activities. Design: The study was conducted from March to December 2015 with volunteer general practices from a range of Australian primary care settings. We used a mixed-methods approach in two parts. Part 1 involved staff in Australian primary care practices assessing how they perceived their practice met (or did not meet) each of the 13 PC-PIT elements of high-performing practices, using a 1–5 Likert scale. In Part 2, two external raters conducted an independent practice visit to independently and objectively assess the subjective practice assessment from Part 1 against objective indicators for the 13 elements, using the same 1–5 Likert scale. Concordance between the raters was determined by comparing their ratings. In-depth interviews conducted during the independent practice visits explored practice managers’ experiences and perceived support and resource needs to undertake organisational improvement in practice. Results: Data were available for 34 general practices participating in Part 1. For Part 2, independent practice visits and the inter-rater comparison were conducted for a purposeful sample of 19 of the 34 practices. Overall concordance between the two raters for each of the assessed elements was excellent. Three practice types across a continuum of higher- to lower-scoring practices were identified, with each using the PC-PIT in a unique way. During the in-depth interviews, practice managers identified benefits of having additional QI tools that relate to the PC-PIT elements. Conclusions: The PC-PIT is an organisational performance tool that is acceptable, valid and relevant to our range of partners and the end users (general practices). Work is continuing with our partners and end users to embed the PC-PIT in existing organisational improvement programs.
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This study examines how sex education is currently developed and implemented in Greek primary schools. The four publications that comprise it explore the following themes: (1) the position and visibility of sex education as one of the topics for health education programme development; (2) the inhibiting and enhancing factors in the development and implementation of primary school sex education programmes; (3) how issues of sex, sexuality, the human body and romantic relationships are visually and textually represented in primary school textbooks; (4) the impact of sex education on teachers and pupils; and (5) teachers experiences as practitioners who deal with sexuality- related issues at school. -- The research was based on conducting multiple sub-studies using a mixed-methods approach. Specifically, qualitative and quantitative data were collected and analysed. The initial quantitative data that had been obtained by questionnaire was followed by the collection and analysis of qualitative data. The qualitative data were acquired by way of examining one particular case, various texts, interviews with teachers and self-reflective material. The results of the sub-studies are presented in a more detailed manner in the study s four publications. -- In general, the sub-studies found that sex education as an educational activity occupies a marginal place within the instructional practices of Greek primary school teachers, since the subject is hardly mentioned in classroom material, such as textbooks. However, engaging in the provision of sex education programmes can become a meaningful and rewarding experience for many teachers as well as pupils and their families. Further, teachers classroom experiences pointed to school settings as sexualized environments. These contextual factors and conditions nevertheless affected teachers practices and perceptions on a personal and professional level.Health indicators in Greece provide a picture of a population that faces various sexual health related problems. However, as many studies (including this work) indicate, sex education programmes that meet specific standards can have a positive impact on students overall health and well-being. Sex education teaching has always been a controversial issue. Its successful implementation in Greece demands knowledgeable educators and responsible policy-makers. The findings of this study suggest that the content of Greek primary school textbooks needs to be revised in order to include texts and pictures that deal with the human body and human sexuality, encourage pupils to become involved in designing the content and methods of programmes and give teachers the opportunity to reflect on and discuss their experiences. Keywords: sex education, primary school, Greece
Resumo:
There is considerable evidence that children in modern society are losing
their contact with nature and, more precisely, with green plants. Is this also the case in Finland, a northern country famous for its forests and wild nature? This study examines the relationship of 9- to 10-year-old Finnish schoolchildren with the green environment and plants. The data were gathered by a questionnaire
comprising structured and open-ended questions. The focus of the research was on two comparisons: first, on the nature and child relationship in rural and urban neighborhoods and, second, among boys and girls. Participants in the study amounted to a total of 76 children, 42 in the Helsinki suburb area and 34 in Paltamo. The results suggested that the children in rural surroundings had closer contact with nature than their urban associates. For example, the children of Paltamo reported to know the trees better, and considered human beings to be part of nature more often (100% vs. 76% of the pupils in Helsinki, P = 0,003). Similarly, the results showed that girls in the study (N = 48) were more interested in plants than boys (N = 28). For the girls, the beauty and joy of plants was important, whereas the boys appreciated plants as the source of life. After the pre-questioning, the children of Helsinki participated in an in-class horticultural intervention and 10 days later, answered a similar questionnaire again. The results of the open-ended questions revealed that equally to children in other Western countries, Finnish children may also be in danger of losing their direct contact with the natural environment. It was common to pass free time in organized sports such as hockey or football (boys), or by just walking and talking with friends (girls). Rural children told that they still built huts, pick berries, and climb trees, whereas urban children played in parks and city groves. The results suggest that it is essential to research
further the children’s own experiences if we are to understand, and subsequently, to enhance, the crucial role of the green environment in their lives. Horticultural interventions can be effective starting points to add to children’s knowledge, affection, and interest toward greenery, but it is highly recommended that they take place outdoors rather than indoors.
Resumo:
There is considerable evidence that children in modern society are losing
their contact with nature and, more precisely, with green plants. Is this also the case in Finland, a northern country famous for its forests and wild nature? This study examines the relationship of 9- to 10-year-old Finnish schoolchildren with the green environment and plants. The data were gathered by a questionnaire
comprising structured and open-ended questions. The focus of the research was on two comparisons: first, on the nature and child relationship in rural and urban neighborhoods and, second, among boys and girls. Participants in the study amounted to a total of 76 children, 42 in the Helsinki suburb area and 34 in Paltamo. The results suggested that the children in rural surroundings had closer contact with nature than their urban associates. For example, the children of Paltamo reported to know the trees better, and considered human beings to be part of nature more often (100% vs. 76% of the pupils in Helsinki, P = 0,003). Similarly, the results showed that girls in the study (N = 48) were more interested in plants than boys (N = 28). For the girls, the beauty and joy of plants was important, whereas the boys appreciated plants as the source of life. After the pre-questioning, the children of Helsinki participated in an in-class horticultural intervention and 10 days later, answered a similar questionnaire again. The results of the open-ended questions revealed that equally to children in other Western countries, Finnish children may also be in danger of losing their direct contact with the natural environment. It was common to pass free time in organized sports such as hockey or football (boys), or by just walking and talking with friends (girls). Rural children told that they still built huts, pick berries, and climb trees, whereas urban children played in parks and city groves. The results suggest that it is essential to research
further the children’s own experiences if we are to understand, and subsequently, to enhance, the crucial role of the green environment in their lives. Horticultural interventions can be effective starting points to add to children’s knowledge, affection, and interest toward greenery, but it is highly recommended that they take place outdoors rather than indoors.
Resumo:
In Finland, there is a desperate need for flexible, reliable and functional multi-e-learning settings for pupils aged 11-13. Southern Finland has several ongoing e-learning projects, but none that develop a multiple setting, with learning and teaching occurring between more than two schools. In 2006, internet connections were not broadband and data transfer was mainly audio data. Connections and technical problems occurred, which were an obstacle to multi-e-learning. Internet connections today enable web-based learning in major parts of
Lapland and by 2015, broadband will reach even the remotest villages up north. Therefore, it is important to research the possibilities of multi-e-learning and to build collaborative, learner-centred, versatile network models for primary school-aged pupils. The resulting model will facilitate distance learning to extend education to rural, sparsely populated areas, and it will give a model of using mobile devices in language portfolios. This will promote regional equality and prevent exclusion. Working with portfolios provides the opportunity to develop mobility from a pedagogical point of view. It is important to study the pros and cons of mobile devices in producing artefacts on portfolios in e-learning and language learning settings.
The current study represents a design-based research approach. The design research approach includes two important aspects concerning the current research: ‘a teacher as researcher’ aspect, which means there is the possibility to be strongly involved in developing processes and an obstacle-aspect, which means that problems while developing, are seen as a
promoter in evolving the designed model, as apposed to negative results.
Resumo:
There is considerable evidence that children in modern society are losing
their contact with nature and, more precisely, with green plants. Is this also the case in Finland, a northern country famous for its forests and wild nature? This study examines the relationship of 9- to 10-year-old Finnish schoolchildren with the green environment and plants. The data were gathered by a questionnaire
comprising structured and open-ended questions. The focus of the research was on two comparisons: first, on the nature and child relationship in rural and urban neighborhoods and, second, among boys and girls. Participants in the study amounted to a total of 76 children, 42 in the Helsinki suburb area and 34 in Paltamo. The results suggested that the children in rural surroundings had closer contact with nature than their urban associates. For example, the children of Paltamo reported to know the trees better, and considered human beings to be part of nature more often (100% vs. 76% of the pupils in Helsinki, P = 0,003). Similarly, the results showed that girls in the study (N = 48) were more interested in plants than boys (N = 28). For the girls, the beauty and joy of plants was important, whereas the boys appreciated plants as the source of life. After the pre-questioning, the children of Helsinki participated in an in-class horticultural intervention and 10 days later, answered a similar questionnaire again. The results of the open-ended questions revealed that equally to children in other Western countries, Finnish children may also be in danger of losing their direct contact with the natural environment. It was common to pass free time in organized sports such as hockey or football (boys), or by just walking and talking with friends (girls). Rural children told that they still built huts, pick berries, and climb trees, whereas urban children played in parks and city groves. The results suggest that it is essential to research
further the children’s own experiences if we are to understand, and subsequently, to enhance, the crucial role of the green environment in their lives. Horticultural interventions can be effective starting points to add to children’s knowledge, affection, and interest toward greenery, but it is highly recommended that they take place outdoors rather than indoors.
Resumo:
In Finland, there is a desperate need for flexible, reliable and functional multi-e-learning settings for pupils aged 11-13. Southern Finland has several ongoing e-learning projects, but none that develop a multiple setting, with learning and teaching occurring between more than two schools. In 2006, internet connections were not broadband and data transfer was mainly audio data. Connections and technical problems occurred, which were an obstacle to multi-e-learning. Internet connections today enable web-based learning in major parts of Lapland and by 2015, broadband will reach even the remotest villages up north. Therefore, it is important to research the possibilities of multi-e-learning and to build collaborative, learner-centred, versatile network models for primary school-aged pupils. The resulting model will facilitate distance learning to extend education to rural, sparsely populated areas, and it will give a model of using mobile devices in language portfolios. This will promote regional equality and prevent exclusion. Working with portfolios provides the opportunity to develop mobility from a pedagogical point of view. It is important to study the pros and cons of mobile devices in producing artefacts on portfolios in e-learning and language learning settings. The current study represents a design-based research approach. The design research approach includes two important aspects concerning the current research: ‘a teacher as researcher’ aspect, which means there is the possibility to be strongly involved in developing processes and an obstacle-aspect, which means that problems while developing, are seen as a promoter in evolving the designed model, as apposed to negative results.
Resumo:
This thesis studies the tree species’ juvenile diversity in cacao (Theobroma cacao L.) based agroforestry and in primary forest in a natural conservation forest environment of Lore Lindu National Park, Sulawesi, Indonesia. Species’ adult composition in Lore Lindu National Park is relatively well studied, less is known about tree species’ diversity in seedling communities particularly in frequently disturbed cacao agroforestry field environment. Cacao production forms a potentially serious thread for maintaining the conservation areas pristine and forested in Sulawesi. The impacts of cacao production on natural environment are directly linked to the diversity and abundance of shade tree usage. The study aims at comparing differences between cacao agroforestry and natural forest in the surrounding area in their species composition in seedling and sapling size categories. The study was carried out in two parts. Biodiversity inventory of seedlings and saplings was combined with social survey with farmer interviews. Aim of the survey was to gain knowledge of the cacao fields, and farmers’ observations and choices regarding tree species associated with cacao. Data was collected in summer 2008. The assessment of the impact of environmental factors of solar radiation, weeding frequency, cacao tree planting density, distance to forest and distance to main park road, and type of habitat on seedling and sapling compositions was done with Non-metric Multidimensional Scaling (NMS). Outlier analysis was used to assess distorting variables for NMS, and Multi-Response Permutation Procedures (MRPP) analysis to differentiate the impact of categorical variables. Sampling success was estimated with rarefaction curves and jackknife estimate of species richness. In the inventory 135 species of trees and shrubs were found. Only some agroforestry related species were dominating. The most species rich were sapling communities in forest habitat. NMS was showing generally low linear correlation between variation of species composition and environmental variables. Solar radiation was having most significance as explaining variable. The most clearly separated in ordination were cacao and forest habitats. The results of seedling and sapling inventory were only partly coinciding with farmers’ knowledge of the tree species occurring on their fields. More research with frequent assessment of seedling cohorts is needed due to natural variability of cohorts and high mortality rate of seedlings.
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Purpose: A number of proteome studies have been performed recently to identify pheromone-related protein expression and their molecular function using genetically modified rodents' urine. However, no such studies have used Indian commensal rodents; interestingly, in a previous investigation, we confirmed the presence of volatile molecules in commensal rodents urine and these molecules seem to be actively involved in pheromonal communication. Therefore, the present study aims to identify the major urinary protein [MUP] present in commensal rat urine, which will help us to understand the protein's expression pattern and intrinsic properties among the rodents globally. Experimental Design: Initially, the total urinary proteins were separated by 1-D and 2-D electrophoresis and then subsequently analyzed by Matrix Assisted Laser Desorption Ionization-Time of Flight and Mass Spectrometer (MALDI-TOF/MS). Furthermore, they were then fragmented with the aid of a Tandem Mass Spectrometer (TOF/TOF) and the identified sequences aligned and confirmed using similarity with the deduced primary structures of members of the lipocalin superfamily.Results: The SDS-PAGE protein profiles showed distinct proteins with molecular masses of 15, 22.4, 25, 28, 42, 50, 55, 68, and 91 kDa. Of these proteins, the 22.4 kDa protein was considered to be target candidate. When 2D electrophoresis was carried out, about similar to 50 spots were detected with different masses and various pI ranges. The 22.4 kDa protein was found to have a pI of about 4.9. This 22.4 kDa protein spot was digested and subjected to mass spectrometry; it was identified as rat MUP. The fragmented peptides from the rat MUP at 935, 1026, 1192, and 1303 m/z were further fragmented with the aid of MS/MS and generated de novo sequence and this confirmed this protein to be the MUP present in the urine of commensal rats.Conclusion: The present investigation confirms the presence of MUP with a molecular mass of 22.4 kDa in the urine of commensal rats. This protein may be involved in the binding of volatile molecules and opens up a discussion about how volatile and non-volatile molecules in the commensal rats' urine may contribute chemo-communication.
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The pattern of expression of the genes involved in the utilization of aryl beta-glucosides such as arbutin and salicin is different in the genus Shigella compared to Escherichia coli. The results presented here indicate that the homologue of the cryptic bgl operon of E. coli is conserved in Shigella sonnei and is the primary system involved in beta-glucoside utilization in the organism. The organization of the bgl genes in 5. sonnei is similar to that of E. coli; however there are three major differences in terms of their pattern of expression. (i) The bglB gene, encoding phospho-beta-glucosidase B, is insertionally inactivated in 5. sonnei. As a result, mutational activation of the silent bgl promoter confers an Arbutin-positive (Arb(+)) phenotype to the cells in a single step; however, acquiring a Salicin-positive (Sal(+)) phenotype requires the reversion or suppression of the bglB mutation in addition. (ii) Unlike in E. coli, a majority of the activating mutations (conferring the Arb(+) phenotype) map within the unlinked hns locus, whereas activation of the E. coli bgl operon under the same conditions is predominantly due to insertions within the bglR locus. (iii) Although the bgl promoter is silent in the wild-type strain of 5. sonnei (as in the case of E. coli), transcriptional and functional analyses indicated a higher basal level of transcription of the downstream genes. This was correlated with a 1 bp deletion within the putative Rho-independent terminator present in the leader sequence preceding the homologue of the bglG gene. The possible evolutionary implications of these differences for the maintenance of the genes in the cryptic state are discussed.