基于滤除R波的主导频率算法的房颤心内信号分析

为了进一步探究房颤患者心内不同位置信号的主导频率(Dominant frequency,简称DF)的关联性,本文对传统的Botteron’s算法进行了改进。当信号中含有较大幅值的室波时,该改进算法可以更好地提取DF。利用该算法对20例临床房颤消融手术的冠状静脉窦(Coronary sinus,简称CS)导管、环肺静脉(Pulmonary veins,简称PV)导管采集的信号进行了观察和分析。在大部分病例中都能观察到其CS和PV的信号里都存在相同频率的DF;同时发现CS的DF并不仅仅来自当前标测的PV。实验结果表明:房颤的潜在病灶区域不仅仅具有较高频率的DF,且其DF的频率应当与心房采集的DF频率存在对应关系。这或许可以为寻找房颤的潜在病灶区域提供参考。     

Intensities of drilling predation of molluscan assemblages along a transect through the northern Gulf of Trieste (Adriatic Sea)

Drilling predation is one of the most studied biotic interactions in the fossil record and potentially controls biodiversity, but its history may be confounded by natural patchiness across environments. This aspect has been inconsistently evaluated. The current study contributes to our understanding of drilling predation in the Northern Adriatic, which has been previously classified as a low-predation setting, and examines the roles of environment, patchiness, and ecology of prey organisms in modern seas. Nearly 49,000 molluscs from two intertidal and six sublittoral bulk samples along a transect in the Gulf of Trieste were analysed for drill frequency (DF) and prey effectiveness (PE), a measure of prey's ability to resist predatory attacks.DF across all samples was 20.6%, but varied between the intertidal (1.4%) and sublittoral (27.4%). Among the latter, DF differed between the delta foreset beds (18.1%) and level bottom muds and sands (～ 28% each). PE was low in the intertidal (1.1%) and sublittoral (4.5%). Overall DF and PE among the three mud samples varied by nearly 10%, while that within the two sand samples varied little; however, significantly different DFs were observed only among the families Nuculidae, Galeommatidae and Corbulidae in level bottom mud and Cerithiidae in level bottom sand samples. Only Corbulidae displayed significant variation in PE among level bottom mud samples (16.5–43.7%). PE varied significantly between level bottom sand samples only within the families Cerithiidae and Trochidae.Suspension-feeding bivalves and gastropods had the highest DFs (24.3% and 39.1%, respectively), and the value of epifaunal bivalves (32.0%) was nearly twice as high as that of infaunal bivalves (17.9%). DFs of cementing (43.0%) and byssate (27.0%) bivalves were higher than that of recliners (9.9%). Considering their cryptic life habits, parasitic gastropods (20.3%) and commensal bivalves (40.6%) had exceptionally high DF. For each ecological category, PE was highest on suspension-feeding (11.1%), infaunal (15.8%) and cementing (10.5%) bivalves, and on parasitic gastropods (11.9%).DF did not correlate with diversity indices or predator abundance in the sublittoral; therefore, drilling predation probably does not control diversity on the local scale here. DFs support paleoecological theory relating predation to changes in ecological guilds through the Phanerozoic. DFs were highest on suspension feeders, parasites and sessile prey, and were lowest on predators, recliners, and endobenthic molluscs. While cementation likely reduces bivalve susceptibility to durophages, it apparently does not to impede drilling predators. Finally, DF did not vary across size classes in any species examined except Venerupis rhomboides, where the smallest fraction was drilled more often. Additionally, as the proportion of large individuals in our samples was small, disparities in DF across size classes probably did not influence our results. With respect to predation intensity the relatively high DF in the sublittoral, as well as high DF and PE for various taxa and guilds, places the Northern Adriatic Sea among typical Cenozoic shelf environments.     

Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling

Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.     

Selecting discriminant function models for predicting the expected richness of aquatic macroinvertebrates

1. The predictive modelling approach to bioassessment estimates the macroinvertebrate assemblage expected at a stream site if it were in a minimally disturbed reference condition. The difference between expected and observed assemblages then measures the departure of the site from reference condition. 2. Most predictive models employ site classification, followed by discriminant function (DF) modelling, to predict the expected assemblage from a suite of environmental variables. Stepwise DF analysis is normally used to choose a single subset of DF predictor variables with a high accuracy for classifying sites. An alternative is to screen all possible combinations of predictor variables, in order to identify several ‘best’ subsets that yield good overall performance of the predictive model. 3. We applied best‐subsets DF analysis to assemblage and environmental data from 199 reference sites in Oregon, U.S.A. Two sets of 66 best DF models containing between one and 14 predictor variables (that is, having model orders from one to 14) were developed, for five‐group and 11‐group site classifications. 4. Resubstitution classification accuracy of the DF models increased consistently with model order, but cross‐validated classification accuracy did not improve beyond seventh or eighth‐order models, suggesting that the larger models were overfitted. 5. Overall predictive model performance at model training sites, measured by the root‐mean‐squared error of the observed/expected species richness ratio, also improved steadily with DF model order. But high‐order DF models usually performed poorly at an independent set of validation sites, another sign of model overfitting. 6. Models selected by stepwise DF analysis showed evidence of overfitting and were outperformed by several of the best‐subsets models. 7. The group separation strength of a DF model, as measured by Wilks’Λ, was more strongly correlated with overall predictive model performance at training sites than was DF classification accuracy. 8. Our results suggest improved strategies for developing reliable, parsimonious predictive models. We emphasise the value of independent validation data for obtaining a realistic picture of model performance. We also recommend assessing not just one or two, but several, candidate models based on their overall performance as well as the performance of their DF component. 9. We provide links to our free software for stepwise and best‐subsets DF analysis.     

Changing dendritic field size of mouse retinal ganglion cells in early postnatal development

During early postnatal development, dendrites of retinal ganglion cells (RGCs) extend and branch in the inner plexiform layer to establish the adult level of stratification, pattern of branching, and coverage. Many studies have described the branching patterns, transient features, and regulatory factors of stratification of the RGCs. The rate of RGC dendritic field (DF) expansion relative to the growing retina has not been systematically investigated. In this study, we used two methods to examine the relative expansion of RGC DFs. First, we measured the size of RGC DFs and the diameters of the eyeballs at several postnatal stages. We compared the measurements with the RGC DF sizes calculated from difference of the eyeball sizes based on a linear expansion assumption. Second, we used the number of cholinergic amacrine cells (SACs) circumscribed by the DFs of RGCs at corresponding time points as an internal ruler to assess the size of DFs. We found most RGCs exhibit a phase of faster expansion relative to the retina between postnatal day 8 (P8) and P13, followed by a phase of retraction between P13 and adulthood. The morphological α cells showed the faster growing phase but not the retraction phase, whereas the morphological ON–OFF direction selective ganglion cells expanded in the same pace as the growing retina. These findings indicate different RGCs show different modes of growth, whereas most subtypes exhibit a fast expansion followed by a retraction phase to reach the adult size. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 70: 397–407, 2010     

Homoplasy and the delineation of holophyletic genera in some insect groups

Abstract. Some groups of insects, such as certain Ichneumonidae and fungus-feeding Phlaeothripidae, appear to have undergone frequent reversal or parallelism (homoplasy) of characters during evolution so that extant species present almost every imaginable permutation and combination of characters. Recognition of holophyletic genera in such groups is difficult. Large monothetically defined genera are often not holophyletic, whilst small genera need to be defined by a large and invariable character-suite. Any classification produced by adopting small genera will not possess one of the valuable attributes of the classical Linnaean system, its predictive ability; a large proportion of new species will require new genera. For groups exhibiting a high degree of homoplasy it is suggested that a polythetic classification be erected. Polythetic genera can be holophyletic groups and are not merely phenetic assemblages. The probability of correctly assigning a species (either a new one or when making an identification) is shown to be higher for a polythetic classification. A simple key device, the polyclave, is given to enable practical separation of two polythetic taxa. It is suggested that homoplasy, and its associated problems in classification, may be associated with a particular type of biology in which population size is not limited by direct competition.     

Development of a classification and ranking method for the identification of possible biomarkers in two-dimensional gel-electrophoresis based on principal component analysis and variable selection procedures

The identification of biomarkers is one of the leading research areas in proteomics. When biomarkers have to be searched for in spot volume datasets produced by 2D gel-electrophoresis, problems may arise related to the large number of spots present in each map and the small number of samples available in each class (control/pathological). In such cases multivariate methods are usually exploited together with variable selection procedures, to provide a set of possible biomarkers: they are however usually aimed to the selection of the smallest set of variables (spots) providing the best performances in prediction. This approach seems not to be suitable for the identification of potential biomarkers since in this case all the possible candidate biomarkers have to be identified to provide a general picture of the "pathological state": in this case exhaustivity has to be preferred to provide a complete understanding of the mechanisms underlying the pathology. We propose here a ranking and classification method, "Ranking-PCA", based on Principal Component Analysis and variable selection in forward search: the method selects one variable at a time as the one providing the best separation of the two classes investigated in the space given by the relevant PCs. The method was applied to an artificial dataset and a real case-study: Ranking-PCA exhaustively identified the potential biomarkers and provided reliable and robust results.     

Spectrum of MHC class II variability in Darwin's finches and their close relatives

The study describes >400 major histocompatibility complex (MHC) class II B exon 2 and 114 intron 2 sequences of 36 passerine bird species, 13 of which belong to the group of Darwin's finches (DFs) and the remaining 23 to close or more distant relatives of DFs in Central and South America. The data set is analyzed by a combination of judiciously selected statistical methods. The analysis reveals that reliable information concerning MHC organization, including the assignment of sequences to loci, and evolution, as well as the process of species divergence, can be obtained in the absence of genomic sequence data, if the analysis is taken several steps beyond the standard phylogenetic tree construction approach. The main findings of the present study are these: The MHC class II B region of the passerine birds is as elaborate in its organization, divergence, and genetic diversity as the MHC of the eutherian mammals, specifically the primates. Hence, the reported simplicity of the fowl MHC is an oddity. With the help of appropriate markers, the divergence of the MHC genes can be traced deep in the phylogeny of the bird taxa. Transspecies polymorphism is rampant at many of the bird MHC loci. In this respect, the DFs behave as if they were a single, genetically undifferentiated population. There is thus far no indication of alleles that could be considered species, genus, or even DF group specific. The implication of these findings is that DFs are in the midst of adaptive radiations, in which morphological differentiation into species is running ahead of genetic differentiation in genetic systems such as the MHC or the mitochondrial DNA. The radiations are so young that there has not been enough time to sort out polymorphisms at most of the loci among the morphologically differentiating species. These findings parallel those on Lake Victoria haplochromine fishes. Several of the DF MHC allelic lineages can be traced back to the MHC genes of the species Tiaris obscura, which we identified previously as the closest extant relative of DFs in continental America.     

Involvement of apoptosis in the atresia of nonovulatory dominant follicle during the bovine estrous cycle

The present study was designed to 1) investigate whether apoptosis is responsible for the atresia of nonovulatory dominant follicle (DF), 2) to determine if atresia of a nonovulatory DF is associated with alterations in Bcl-2 and Bax expression, 3) to test whether progesterone P(4) has a direct effect on apoptosis in bovine follicles, and 4) to study the pattern of expression of Bcl-2 and Bax in follicles at different developmental stages (small, medium, and large). In experiment 1, 16 cycling cows received a norgestomet ear implant at proestrus (Day 1) for 9 days to mimic the subluteal phase. The cows were assigned either to a control (n = 4) or P(4)-treated groups (n = 12). Injections of P(4) (150 mg, i.m.) were given on Day 3 (n = 4); on Days 3 and 4 (n = 4), and on Days 3, 4, and 5 (n = 4) of the implant period. Controls received injections of corn oil on Days 3, 4, and 5. Unilateral ovariectomy was performed on Days 4, 5, and 6 to recover DFs from cows that had been treated with P(4) for 24, 48, and 72 h, respectively. DFs in the control group were collected on Day 6. The onset of atresia of DFs was assessed morphologically by ultrasound to determine DF diameters, histologically by light microscopic inspection of tissue sections, and functionally by quantification of follicular fluid steroid hormone levels. Apoptosis was detected by DNA analysis and in situ TUNEL labeling. Expression of Bcl-2 and Bax proteins was examined by Western blot analysis. The earliest signs of atresia were detected 24 h after P(4) injection as evidenced by decreased diameter, degeneration and detachment of granulosa cells (GCs) from the basal lamina, and a dramatically reduced ratio of estrogen to P(4). Electrophoretic analysis of DNA extracted from DFs of cows treated with P(4) for 24 h revealed a distinct ladder pattern of DNA fragments. In contrast, this pattern was not obvious in DFs from control cows. Similar results were also obtained from TUNEL analysis of DFs. Furthermore, both Bcl-2 and Bax were found to be present in all DFs; however, the ratio of Bcl-2 and Bax protein levels was significantly reduced by 24 h of P(4) treatment compared with DFs from the control group (P < 0.05). Experiment 2 investigated the direct effect of P(4) (4 ng/ml) on apoptosis of cultured GCs using ovaries obtained from a local slaughterhouse. In addition, the pattern of expressions of Bcl-2 and Bax in follicles at different developmental stages (small, medium, and large) was studied. No increase in apoptotic DNA fragments was detected in GCs treated with P(4). The ratio of Bcl-2 and Bax protein levels was variable in small follicles; however, Bax protein level was always relatively higher than that of Bcl-2 in medium and large follicles. In conclusion, our study suggests that apoptosis is the mechanism that underlies the atresia of nonovulatory DFs that develops during the luteal phase of bovine estrous cycle.     

Intraspecies diversity of dormant forms of <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The non-spore-forming gram-positive bacterium Mycobacterium smegmatis mc² 155, related to M. tuberculosis, was revealed to be capable of forming different types of dormant forms (DFs) during the life cycle of its cultures. The relationship between the intraspecies diversity of DFs and the cultivation conditions of the mycobacterium was established. The DFs possessed the following common properties: (i) maintenance of viability for a long period of time (5 months), (ii) resistance to deleterious factors such as heat treatment, and (iii) morphological and ultrastructural peculiarities that distinguish DFs from vegetative cells. The diversity of M. smegmatis DFs manifested itself in differences in terms of structural organization, conditions required for growth renewal, and capacity to produce antibiotic-resistant variants upon germination on selective media. Well-differentiated cystlike dormant cells (CDCs) were formed in the cultures grown in synthetic SR1 medium with fivefold-decreased nitrogen content. The structural organization of CDCs differed from that of other DF types mainly in the presence of club-shaped cells, thickened lamellar cell walls, coarse cytoplasm texture, and large electron-transparent triacylglyceride inclusion bodies. It was possible to use mycobacterial CDCs as a source of PCR-competent DNA. CDC populations were heterogeneous in cell buoyant density, and the individual fractions, which we isolated, were found to differ in thermal stability and the ability to revert to growth under standard conditions. Coccoid DFs, which retained their colony-forming capacity for a long time but were less heat-resistant than the CDCs, were formed by mycobacteria grown in standard Sauton’s medium with initial pH value decreased to 6.2. Poorly differentiated DFs resulted from growing mycobacterial cultures in Sauton’s medium with a fivefold-decreased phosphorus content. Upon germination of various DF types, the variants resistant to kanamycin (200 μg/ml) and tetracycline (20 μg/ml) were obtained. CDC suspensions incubated for 5 months demonstrated the highest percentage (1.5%) of antibiotic-resistant clones. The data obtained on the DF diversity of M. smegmatis, a fast-growing relative of M. tuberculosis, contribute to our understanding of the flexibility of the survival strategy of this bacterium in nature and in the host organism.     

DNA barcoding should accompany taxonomy - the case of Cerebratulus spp (Nemertea)

Many issues in DNA barcoding need to be solved before it can reach its goal to become a general database for species identification. While species delimitations are more or less well established in several taxa, there are still many groups where this is not the case. Without the proper taxonomic background/knowledge and corroboration with other kinds of data, the DNA barcoding approach may fail to identify species accurately. The classification and taxonomy of phylum Nemertea (nemerteans, ribbon worms) are traditionally based on morphology, but are not corroborated by an increasing amount of genetic data when it comes to classification either into species or into higher taxa. The taxonomy of the phylum needs to be improved before the full potential of DNA barcoding can be utilized to make sure that valid Linnean names accompany the barcode sequences. We illustrate the problematic situation in the phylum Nemertea by a case study from the genus Cerebratulus.     

In vitro formation of lacuna structure by human dermal fibroblasts co-cultured with porcine chondrocytes on a 3D biodegradable scaffold

Dermal fibroblasts (DF) possess chondrogenic differentiation potential but whether DF, or a subpopulation of DF, can form a typical cartilage structure in culture is unknown. In this study, human DF were co-cultured with porcine articular chondrocytes on a biodegradable scaffold of polylactic acid/polyglycolic acid. Histological analysis demonstrated that some DFs can be induced to form cartilage lacuna structure showing the existence of a chondrogenic subpopulation of human DF. Moreover, the 3D-co-culture system can serve as an optimal model for directing stem cell differentiation in vitro. Xia Liu and Guangdong Zhou contributed equally to this work.     

Computer modelling of maximal displacement forces in endoluminal thoracic aortic stent graft

The objective of this study was to determine the orientation and magnitude of maximal displacement forces (DFs) in the thoracic aortic aneurysm endograft (TAA endograft) in three-dimensional (3D) space. Theoretical computer model representing the anatomically worst-case scenario with respect to DF magnitude was used to calculate the magnitude and orientation of maximal DF. A patient-specific anatomical computer model of typically seen, average size anatomy was used to analyse the progression of DF throughout the cardiac cycle. Maximal DFs were 35.01 and 37.32 N in standing and supine position, respectively, in 46-mm diameter TAA graft with 90° bend. A patient-specific model shows that a maximal DF magnitude is achieved at the peak systolic flow. In both models, the orientation of the DF vector was perpendicular to the greater curvature of the aorta, with upward (cranial) and sideways components. The effect of shearing force on the total DF that acts on the TAA endograft was found negligible due to the several orders of magnitude stronger contribution of pressure forces to the total DF relative to the wall shear stress contribution, resulting in aortic diameters and angulation being the main drivers of DF. It was discovered that the TAA endografts can be subjected to much stronger DF than previously suspected. The magnitude of maximal DF in thoracic aorta in the worst-case scenario could be as high as 35.01 N (standing) and 37.32 N (supine). This new information should be used in the process of designing new generations of TAA endografts with better migration resistance properties.     

Sclerotic fibroma-like dermatofibroma: an uncommon distinctive variant of dermatofibroma

Dermatofibroma (DF) is a common benign cutaneous tumor with many variants based on alterations in the morphology and composition of its diverse elements. One very infrequent type is sclerotic fibroma-like DF (SF-DF). We report 7 new cases of SF-DF. In addition, their main clinicopathological and immunohistochemical features were compared with 14 unselected common DFs and with 3 sclerotic fibromas (SFs). Microscopically, the 7 cases of SF-DFs showed an unencapsulated, well-circumscribed, hypocellular central nodule with thick collagen bundles arranged in a storiform pattern with prominent clefts. The overlying epidermis was attenuated. The periphery of this nodule was more cellular with histopathologic features of common DF. The 7 SF-DFs patients were 4 women and 3 men with a mean (+/-SD) age of 44.8 (+/-15.5) years. These 7 patients were younger than those suffering from SFs [71.0 (+/-17.3) years; (p=0.04)] and older than those presenting common DFs [30.5 (+/-12.3) years; (p=0.03)]. Immunohistochemically, spindle cells in all 7 SF-DFs were negative for CD34 and CD99. On the contrary, the 3 cases of SF were positive for CD34 and CD99. All of the common DFs were negative for CD34 and only 4 (28.6%) of them were positive for CD99. In conclusion, SF-DF is an uncommon variant of DF with similar clinicopathological and immunohistochemical features. SF-DF shares certain histopathologic features with SF but they are immunophenotypically different. Therefore, both entities should be differentiated.     

Development of human health damage factors for tropospheric ozone considering transboundary transport on a global scale

Purpose

Air pollutants such as tropospheric ozone and PM_2.5 travel through large areas. The damage factors (DFs) presented by existing researches in life cycle impact assessment do not take into consideration transboundary movement. A previous study used a global chemistry transport model (CTM), to develop health damage factors for ten different regions around the world by considering the transboundary movement of PM_2.5. Under the same assessment procedure, this research is designed to calculate the ozone DFs by region and to find the effects of wide range movement on the DFs.

Methods

The DFs by regions are defined as changes in disability-adjusted life years (DALYs) derived from changes in tropospheric ozone concentration around the world which is induced by an increase in emissions of the unit amount of nitrogen oxides (NO_x) and non-methane volatile organic compounds (NMVOC). DFs for ten regions are calculated as follows. Firstly, the concentration change of worldwide ozone caused by a change in emission of a substance from one region is estimated with a global scale CTM for both NO_x and NMVOC. Secondly, DALY changes on the world due to a change in concentration of ozone are estimated by using population data and epidemiological concentration-response functions for mortality and morbidity. Finally, the above calculations are done for all targeted ten regions.

Results and discussion

DFs of NO_x and NMVOC for ten regions were calculated as 0.3–4.2?×?10^?5 DALY/kg and 0.2–5.6?×?10^?6 DALY/kg, respectively. It was found DFs might be underestimated around 10 to 70 % by region if the transboundary movement is not taken into consideration. In many regions in the northern hemisphere, about 60 % of damage occurs outside the emission area, which is larger than that of southern hemispheric regions due to a larger population exposed to downwind places. In regions of China and India, however, the influence on other regions accounted for only 10 % because these regions involve larger influences in the source region. The impact of NO titration effect can be seen in cold seasons in many regions, but it was found that the effect is remarkable on an annual average only in Europe, a cold region with large emissions.

Conclusions

The human health DFs of NO_x and NMVOC considering effects of transboundary movement of tropospheric ozone are estimated for ten regions by using a global CTM. As a future work, it is important to show the interannual sensitivity of the DFs through chronological assessments.

     

CFTR molecular analysis reveals infrequent allele frequencies in nine cystic fibrosis patients from São Paulo State, Brazil

Although cystic fibrosis (CF) is the most common autosomal recessive disorder in whites, it is thought to be relatively rare or, alternatively, underdiagnosed in Latin America. In Brazil, different groups have shown a DF508 mutation frequency ranging from 30.7% to 50.8%. Such variation may be explained by the ethnic differences observed in this country, which is genetically very heterogeneous. We describe the molecular analysis for 32 mutations of the CFTR gene in nine unrelated patients with cystic fibrosis from S?o Paulo State, Brazil. The main observation of this study was the absence of 30 out of the 32 mutations in 12 alleles among these patients. Except for mutations DF508 and N1303K, no other mutation could be detected in any of the studied patients. In one of two alleles, a DF508 mutation was detected in four patients (22% of the total sample) and an N1303K mutation was detected in two patients (11% of the total sample). One patient was a compound heterozygote for DF508/N1303K. Although the sample studied here was small, it may be possible that our patients have infrequent alleles once these can occur at higher frequencies in selected populations and also show relevant regional differences. Additional investigations in a larger sample are currently in progress in our laboratory to confirm our results, and further studies are still needed to determine the frequencies of CF gene mutations in different regions and ethnic groups in the Brazilian population.     

Development of human health damage factors for PM<Subscript>2.5</Subscript> based on a global chemical transport model

Purpose

Health damage from ambient fine particulate matter (PM_2.5) shows large regional variations and can have an impact on a global scale due to its transboundary movement. However, existing damage factors (DFs) for human health in life cycle assessments (LCA) are calculated only for a few limited regions based on various regional chemical transport models (CTMs). The aim of this research is to estimate the human health DFs of PM_2.5 originating from ten different regions of the world by using one global CTM.

Methods

The DFs express changes in worldwide disability-adjusted life years (DALYs) due to unit emission of black carbon and organic carbon (BCOC), nitrogen oxides (NO _x ), and sulfur dioxide (SO₂). DFs for ten regions were calculated as follows. Firstly, we divided the whole world into ten regions. With a global CTM (MIROC-ESM-CHEM), we estimated the concentration change of PM_2.5 on the world caused by changes in the emission of a targeted precursor substance from a specific region. Secondly, we used population data and epidemiological concentration response functions (CRFs) of mortality and morbidity to estimate changes in the word’s DALYs occurring due to changes in the concentration of PM_2.5. Finally, the above calculations were done for all ten regions.

Results and discussion

DFs of BCOC, NO _x , and SO₂ for ten regions were estimated. The range of DFs could be up to one order of magnitude among the ten regions in each of the target substances. While population density was an important parameter, variation in transport of PM_2.5 on a continental level occurring due to different emission regions was found to have a significant influence on DFs. Especially for regions of Europe, Russia, and the Middle East, the amount of damage which occurred outside of the emitted region was estimated at a quarter, a quarter, and a third of their DFs, respectively. It was disclosed that the DFs will be underestimated if the transboundary of PM_2.5 is not taken into account in those regions.

Conclusions

The human health damage factors of PM_2.5 produced by BCOC, NO _x , and SO₂ are estimated for ten regions by using one global chemical transport model. It became clear that the variation of transport for PM_2.5 on a continental level greatly influences the regionality in DFs. For further research to quantify regional differences, it is important to consider the regional values of concentration response function (CRF) and DALY loss per case of disease or death.

     

The Middle Ear--Morphological Types in Amphibians and Reptiles

The middle ear regions of reptiles and amphibians frequentlyare grouped into morphological types on the basis of structuralresemblances. The arrays of animals resulting from such a groupinghave a fair degree of taxonomic continuity. The types in mostinstances include a "central" pattern, presumed to be primitive,and modifications that are considered to have been derived fromthe "central" type by evolutionary processes. Some understandingof phylogeny, thus, is a necessary precursor to the formationof the groups. This raises problems when, as is often the case,the groups based on ear structures are used as a basis for phylogeneticinterpretations. Among reptiles the theropsid-sauropsid caseis the best known. The principal morphological types are described and discussed.The middle ear, as a sound-transmitting apparatus and in itsassociations with the masticatory apparatus, is highly susceptibleto adaptive modifications. Some morphological types, such asthose in archosaurs and labyrinthodonts, are quite stable. Othersshow marked evolutionary diversity. The middle ear structures,hence, appear quite useful as phylogenetic indicators withinmorphological types but less so when relationships between typesare considered.     

Metabolic profiling in validation of plasma biomarkers for green tea polyphenols

Green tea polyphenols (GTP) effectively protect against chronic diseases in various animal models but human studies have been inconclusive. GTP components and metabolites in body fluids have been suggested as potential biomarkers, but validation of these biomarkers has rarely been done in human populations. A randomized, double-blinded, and placebo-controlled phase IIa chemoprevention study with GTP was conducted in 120 human subjects for 3 months. To validate GTP biomarker profiles, plasma samples were collected at baseline, 1-month, and 3-month and were analyzed by HPLC-Coularray electrochemical detection (ECD) for specific GTP components as well as for non-targeted metabolites. The levels of 2 GTP components, epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), were homogenous at baseline (p > 0.45) but were significantly elevated (p < 0.01) by GTP treatment. Metabolic profiling identified 106 metabolites, and 56 of them were chosen to construct discriminant functions (DFs) based on the data at 3 months. The DFs clearly separated the placebo, 500 mg GTP, and 1000 mg GTP groups with an accuracy rate of 97.3%. When the DFs were applied to the combined baseline and 1-month data, the accuracy rate was 62.9% in classifying subjects into the 3 intervention groups. DFs derived from 1-month data showed similar results. Overall, this study validated plasma EGCG and ECG as reliable biomarkers for GTP consumption, and found metabolic profiles effective in discriminating different GTP dosages.     

Endocrine regulation of ovarian antral follicle development in cattle

Antral follicle growth in cattle occurs in two distinct phases; the first 'slow' growth phase spans the time from antrum acquisition to a size of approximately 3 mm detectable by transrectal ultrasound, and the second 'fast' phase is gondadotrophin-dependent and includes cohort growth, dominant follicle (DF) selection, and DF growth. This review summarises current concepts of the relative roles FSH and LH, ovarian and metabolic hormones play mainly in the second phase of antral follicle growth in animals of different reproductive and nutritional states. It is proposed that differential FSH response may enable one cohort follicle to become selected, and that follicular secretions, particularly inhibin, suppress FSH and thus are responsible for DF selection and dominance. Acute dependence of the DF on LH pulses will determine DF lifespan, and the LH pulse profile can be influenced by metabolic hormones such as leptin, providing one possible link for nutritional state and reproduction. Direct ovarian effects of acute and chronic changes in growth hormone, insulin and insulin-like growth factor (IGF)-I have been described on cohort follicles, DF oestrogen activity and on DF growth. Influences of metabolic hormones on early antral follicles undergoing their first 'slow' growth phase are less well described, yet metabolic hormones appear to enhance growth into the cohort available for FSH-induced emergence, and may influence subsequent developmental competence of oocytes.