GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.

"Are there any right or wrong answers in teaching philosophy": ethics, epistemology, and philosophy in the classroom

This article assesses undergraduate teaching students’ assertion that there are no right and wrong answers in teaching philosophy. When asked questions about their experiences of philosophy in the classroom for primary children, their unanimous declaration that teaching philosophy has ‘no right and wrong answers’ is critically examined across the three sub-disciplinary areas to which they were generally referring, namely, pedagogy, ethics, and epistemology. From a pedagogical point of view, it is argued that some teaching approaches may indeed be more effective than others, and some pupils’ opinions less defensible, but pedagogically, in terms of managing the power relations in the classroom, it is counter-productive to continually insist on notions of truth and falsity at every point. From an ethical point of view, it is contended that anti-realist approaches to meta-ethics may represent a viable intellectual position, but from the point of view of normative ethics, notions of right and wrong still retain significant currency. From an epistemological point of view, it is argued using Karl Poppers’ work that while it may be difficult to determine what constitutes a right answer, determining a wrong one is far more straightforward. In conclusion, it is clear that prospective teachers engaging in philosophy in the classroom, and also future teachers in general, require a far more nuanced philosophical understanding of the notions of right and wrong and truth and falsity. In view of this situation, it we wish to promote the effective teaching of philosophical thinking to children, or produce educators who can understand the conceptual limits of the claims they make and their very real and often serious practical and social consequences, it is recommended that philosophy be reinstated to a fundamental, foundational place within the pre-service teaching curriculum.

Genetics of brain fiber architecture and intellectual performance

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a 2 = 0.55, p = 0.04, left; a 2 = 0.74, p = 0.006, right), bilateral parietal (a 2 = 0.85, p < 0.001, left; a 2 = 0.84, p < 0.001, right), and left occipital (a 2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto- occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.

Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) using genome-wide search

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10 -6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

Association between glaucoma and at–fault motor vehicle collision involvement among older drivers

Objective To examine the association between glaucoma and motor vehicle collision (MVC) involvement among older drivers, including the role of visual field impairment that may underlie any association found. Design A retrospective population-based study Participants A sample of 2,000 licensed drivers aged 70 years and older who reside in north central Alabama. Methods At-fault MVC involvement for five years prior to enrollment was obtained from state records. Three aspects of visual function were measured: habitual binocular distance visual acuity, binocular contrast sensitivity and the binocular driving visual field constructed from combining the monocular visual fields of each eye. Poisson regression was used to calculate crude and adjusted rate ratios (RR) and 95% confidence intervals (CI). Main Outcomes Measures At-fault MVC involvement for five years prior to enrollment. Results Drivers with glaucoma (n = 206) had a 1.65 (95% confidence interval [CI] 1.20-2.28, p = 0.002) times higher MVC rate compared to those without glaucoma after adjusting for age, gender and mental status. Among those with glaucoma, drivers with severe visual field loss had higher MVC rates (RR = 2.11, 95% CI 1.09-4.09, p = 0.027), whereas no significant association was found among those with impaired visual acuity and contrast sensitivity. When the visual field was sub-divided into six regions (upper, lower, left, and right visual fields; horizontal and vertical meridians), we found that impairment in the left, upper or lower visual field was associated with higher MVC rates, and an impaired left visual field showed the highest RR (RR = 3.16, p = 0.001) compared to other regions. However, no significant association was found in deficits in the right side or along the horizontal or vertical meridian. Conclusions A population-based study suggests that older drivers with glaucoma are more likely to have a history of at-fault MVC involvement than those without glaucoma. Impairment in the driving visual field in drivers with glaucoma appears to have an independent association with at-fault MVC involvement, whereas visual acuity and contrast sensitivity impairments do not.

Kansanomainen moraali : Tutkimus savolaisista ja pohjalaisista uskomustarinoista

In my research I discuss belief legends as representations of folk morals. Doing wrong is not one s private affair because it can have consequences for the life of a whole community, and therefore, it is in a community s interest to control the conduct of its members. Belief legends have served as a means of instruction for proper behaviour. In this way a community has contributed to the socialization of its members so as to make them comply with common norms and morals. My study is focused on belief legends relating to some type of offence (a crime, an infringement or another kind of misdeed) and its consequences. I try to find out whether there are regional differences and similarities. The material consists of 3120 warning legends that have been recorded in the years 1881‒1981, mainly in Southern Savo and Southern Ostrobothnia, partly in Northern Savo and Northern Ostrobothnia. I have collected the material at the Folklore Archives of the Finnish Literature Society. As a research method I apply discourse analysis to outline the schematic model of the legends, the superstructure, and the substance of the legends, the semantic macrostructure. Also I apply quantitative methods such as cross tabulations in order to establish regional differences and similarities in the concentrated and far abstracted semantic macrostructure of the legends. I look for explanations for the perceptions made in, above all, the cultural context but also with the view of the development of judicial history. Warning legends relating to what is wrong or right are clearly an expression of peasant folklore. The most common types of offences are violations of law and transgressions of Christian traditions and of social conduct. Transgression of Christian traditions is the most frequently committed offence in all geographical areas surveyed. Warning legends have an explicit focus on offence committed by a single person. The most common punishing figure in Southern Savo is the Devil, in Southern Ostrobothnia the Dead, in Northern Savo God, and in Northern Ostrobothnia the Dead or God. The most rigid folk morals are manifested in legends from Northern Savo, where narratives of mortal sin are more frequent than in other areas. The influence of the revivalist movements may be alleged in explanation of this phenomenon. According to these legends people living in Southern Savo are the most tolerant of those included in the study, presumably because of a more liberal revivalist movement in this area, called the Friendship movement. In folk morals women are treated more severely than men. Characteristic of the legends from Ostrobothnia is the emphasis on community, while the legends from Savo lay stress on individuality. The legends from Ostrobothnia manifest a more explicit distinction between the offence committed by a woman and one committed by a man than do legends from Savo. An explanation may be found in the prevailing industries, adherent in the division of labour between the sexes, in this region. The legends are man-centric. Women s occupations are connected with home and family, whereas men s fields of activities are wider. Women moralise each other harsher than do men. Folk morals advise people to be moderate in every sense. Through belief legends people are taught to respect human beings and the rest of creation, to obey the Christian religion and God, and to be moderate in search of wealth.

Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis

Common diseases such as endometriosis (ED), Alzheimer's disease (AD) and multiple sclerosis (MS) account for a significant proportion of the health care burden in many countries. Genome-wide association studies (GWASs) for these diseases have identified a number of individual genetic variants contributing to the risk of those diseases. However, the effect size for most variants is small and collectively the known variants explain only a small proportion of the estimated heritability. We used a linear mixed model to fit all single nucleotide polymorphisms (SNPs) simultaneously, and estimated genetic variances on the liability scale using SNPs from GWASs in unrelated individuals for these three diseases. For each of the three diseases, case and control samples were not all genotyped in the same laboratory. We demonstrate that a careful analysis can obtain robust estimates, but also that insufficient quality control (QC) of SNPs can lead to spurious results and that too stringent QC is likely to remove real genetic signals. Our estimates show that common SNPs on commercially available genotyping chips capture significant variation contributing to liability for all three diseases. The estimated proportion of total variation tagged by all SNPs was 0.26 (SE 0.04) for ED, 0.24 (SE 0.03) for AD and 0.30 (SE 0.03) for MS. Further, we partitioned the genetic variance explained into five categories by a minor allele frequency (MAF), by chromosomes and gene annotation. We provide strong evidence that a substantial proportion of variation in liability is explained by common SNPs, and thereby give insights into the genetic architecture of the diseases.

Towards a Critique of the Concept of the Right to Self-Determination in Africa : A Conceptual Examination and the Cases of Western Sahara, Southern Sudan and Eritrea

This thesis examines the right to self-determination which is a norm used for numerous purposes by multiple actors in the field of international relations, with relatively little clarity or agreement on the actual and potential meaning of the right. In international practice, however, the main focus in applying the right has been in the context of decolonization as set by the United Nations in its early decades. Thus, in Africa the right to self-determination has traditionally implied that the colonial territories, and particularly the populations within these territories, were to constitute the people who were entitled to the right. That is, self-determination by decolonization provided a framework for the construction of independent nation-states in Africa whilst other dimensions of the right remained largely or totally neglected. With the objective of assessing the scope, content, developments and interpretations of the right to self-determination in Africa, particularly with regard to the relevance of the right today, the thesis proceeds on two fundamental hypotheses. The first is that Mervyn Frost s theory of settled norms, among which he lists the right to self-determination, assumes too much. Even if the right to self-determination is a human right belonging to all peoples stipulated, inter alia, in the first Article of the 1966 International Human Rights Covenants, it is a highly politicized and context-bound right instead of being settled and observed in a way that its denial would need special justification. Still, the suggested inconsistency or non-compliance with the norm of self-determination is not intended to prove the uselessness or inappropriateness of the norm, but, on the contrary, to invite and encourage debate on the potential use and coverage of the right to self-determination. The second hypothesis is that within the concept of self-determination there are two normative dimensions. One is to do with the idea and practice of statehood, the nation and collectivity that may decide to conduct itself as an independent state. The other one is to do with self-determination as a human right, as a normative condition, to be enjoyed by people and peoples within states that supersedes state authority. These external and internal dimensions need to be seen as complementary and co-terminous, not as mutually exclusive alternatives. The thesis proceeds on the assumption that the internal dimension of the right, with human rights and democracy at its core, has not been considered as important as the external. In turn, this unbalanced and selective interpretation has managed to put the true normative purpose of the right making the world better and bringing more just polity models into a somewhat peculiar light. The right to self-determination in the African context is assessed through case studies of Western Sahara, Southern Sudan and Eritrea. The study asks what these cases say about the right to self-determination in Africa and what their lessons learnt could contribute to the understanding and relevance of the right in today s Africa. The study demonstrates that even in the context of decolonization, the application of the right to self-determination has been far from the consistent approach supposedly followed by the international community: in many respects similar colonial histories have easily led to rather different destinies. While Eritrea secured internationally recognized right to self-determination in the form of retroactive independence in 1993, international recognition of distinct Western Sahara and Southern Sudan entities is contingent on complex and problematic conditions being satisfied. Overall, it is a considerable challenge for international legality to meet empirical political reality in a meaningful way, so that the universal values attached to the norm of self-determination are not overlooked or compromised but rather reinforced in the process of implementing the right. Consequently, this thesis seeks a more comprehensive understanding of the right to self-determination with particular reference to post-colonial Africa and with an emphasis on the internal, human rights and democracy dimensions of the norm. It is considered that the right to self-determination cannot be perceived only as an inter-state issue as it is also very much an intra-state issue, including the possibility of different sub-state arrangements exercised under the right, for example, in the form of autonomy. At the same time, the option of independent statehood achieved through secession remains a mode of exercising and part of the right to self-determination. But in whatever form or way applied, the right to self-determination, as a normative instrument, should constitute and work as a norm that comprehensively brings more added value in terms of the objectives of human rights and democracy. From a normative perspective, a peoples right should not be allowed to transform and convert itself into a right of states. Finally, in light of the case studies of Western Sahara, Southern Sudan and Eritrea, the thesis suggests that our understanding of the right to self-determination should now reach beyond the post-colonial context in Africa. It appears that both the questions and answers to the most pertinent issues of self-determination in the cases studied must be increasingly sought within the postcolonial African state rather than solely in colonial history. In this vein, the right to self-determination can be seen not only as a tool for creating states but also as a way to transform the state itself from within. Any such genuinely post-colonial approach may imply a judicious reconsideration, adaptation or up-dating of the right and our understanding of it in order to render it meaningful in Africa today.

The community of medium-sized carnivores: the interactions between species, habitats and rabies

The composition of the carnivore community influences the different forms of inter-specific interactions. Furthermore, inter-specific interactions of carnivores have important implications for intra-guild competition, epidemiology and strategies of species-specific population management. Zoonooses, such as rabies, are diseases that can be transmitted from wildlife to people. Knowing the ecological characteristics of the species helps us to choose the right preventive actions and to time them accurately. In this thesis, I have studied how raccoon dogs Nyctereutes procyonoides, European badgers Meles meles, red foxes Vulpes vulpes and domestic cats Felis silvestris catus act as members of carnivore community, and how these interactions relate to the transmission risk of rabies. In the study area, these species form a community of medium-sized and rather generalist predators. They live in the same areas, in spatially and temporally overlapping home ranges and use the same habitats and dens and even have similar diets. However, there is no direct evidence of competition. Shared dens point to good tolerance of other species. Numerous observations of animals moving in each other’s proximity give similar clues. However, overlapping home ranges and similar habitat preferences lead to frequent inter-specific contacts, which increase the risk of possible rabies transmission. Also, the new insight of habitat use gained by this study illustrates the similar favouring of deciduous forests and fields by these sympatric medium-sized carnivores, creating a basis for contact zones, i.e. risky habitats for rabies transmission and spread. This study is so far the only simultaneous radio tracking study of raccoon dogs, badgers, foxes and cats. These results give new insight of the interactions in the carnivore community, as well as of the behaviour of each individual species. Also, these results have significant implications for the planning of rabies control. In order to reach viable management decisions, not only one or two species should be taken into consideration, but the whole community. In particular, this changes the perspective to inter-specific contacts, animal densities, densities of individuals susceptible to diseases and the magnitude of preventive actions. Rabies should be considered as a multi-vector disease, at least in Finland and the Baltic states. It is of interest for disease management to be able to model an epizootic with local parameters to reflect the real situation and also to suite best the local management needs.

Lepton masses and flavor violation in the Randall-Sundrum model

Lepton masses and mixing angles via localization of 5-dimensional fields in the bulk are revisited in the context of Randall-Sundrum models. The Higgs is assumed to be localized on the IR brane. Three cases for neutrino masses are considered: (a) The higher-dimensional neutrino mass operator (LH.LH), (b) Dirac masses, and (c) Type I seesaw with bulk Majorana mass terms. Neutrino masses and mixing as well as charged lepton masses are fit in the first two cases using chi(2) minimization for the bulk mass parameters, while varying the O(1) Yukawa couplings between 0.1 and 4. Lepton flavor violation is studied for all the three cases. It is shown that large negative bulk mass parameters are required for the right-handed fields to fit the data in the LH.LH case. This case is characterized by a very large Kaluza-Klein (KK) spectrum and relatively weak flavor-violating constraints at leading order. The zero modes for the charged singlets are composite in this case, and their corresponding effective 4-dimensional Yukawa couplings to the KK modes could be large. For the Dirac case, good fits can be obtained for the bulk mass parameters, c(i), lying between 0 and 1. However, most of the ``best-fit regions'' are ruled out from flavor-violating constraints. In the bulk Majorana terms case, we have solved the profile equations numerically. We give example points for inverted hierarchy and normal hierarchy of neutrino masses. Lepton flavor violating rates are large for these points. We then discuss various minimal flavor violation schemes for Dirac and bulk Majorana cases. In the Dirac case with minimal-flavor-violation hypothesis, it is possible to simultaneously fit leptonic masses and mixing angles and alleviate lepton flavor violating constraints for KK modes with masses of around 3 TeV. Similar examples are also provided in the Majorana case.

Metallic Nanoparticles Arranged in a Helical Geometry: Route Towards Strong and Broadband Chiro-optical Response

Recent advances in nanotechnology have paved ways to various techniques for designing and fabricating novel nanostructures incorporating noble metal nanoparticles, for a wide range of applications. The interaction of light with metal nanoparticles (NPs) can generate strongly localized electromagnetic fields (Localized Surface Plasmon Resonance, LSPR) at certain wavelengths of the incident beam. In assemblies or structures where the nanoparticles are placed in close proximity, the plasmons of individual metallic NPs can be strongly coupled to each other via Coulomb interactions. By arranging the metallic NPs in a chiral (e.g. helical) geometry, it is possible to induce collective excitations, which lead to differential optical response of the structures to right-and left circularly polarized light (e.g. Circular Dichroism - CD). Earlier reports in this field include novel techniques of synthesizing metallic nanoparticles on biological helical templates made from DNA, proteins etc. In the present work, we have developed new ways of fabricating chiral complexes made of metallic NPs, which demonstrate a very strong chiro-optical response in the visible region of the electromagnetic spectrum. Using DDA (Discrete Dipole Approximation) simulations, we theoretically studied the conditions responsible for large and broadband chiro-optical response. This system may be used for various applications, for example those related to polarization control of visible light, sensing of proteins and other chiral bio-molecules, and many more.

The identification and quantification of highly stable 'common hairpin' in the dynamic process of co-transcriptional mRNA folding

In our studies, 88 human mRNA samples were collected from the Integrated Sequence-Structure database and then the dynamic process in co-transcriptional mRNA folding was simulated using the RNAstructure version 4.1 program. Through statistical analyses of the frequencies of occurrence of hairpins, a group of special folding structures-the 'common hairpins'-were identified. These 'common hairpins' have lower energies and occur in all the subsequent folding units that formed in the dynamic folding process. By applying the formulas (1)-(4) of the 'common hairpins' statistical model, 163 'common hairpins' were found, to make up about 7% of the total of 2286 hairpins. Classified studies further show that the 'common hairpins' that were studied may oscillate in the dynamic folding process. However, the hairpin loops of the 'common hairpins' and stems proximal to those 'common hairpins' loops maintain topologically stable structures, while other loops and stems distal to the 'common hairpins' loops are shown to be alterable structures. Strikingly, further studies indicate that the stable structures of these 'common hairpins' may have unbeknown effects on controlling the formation of protein structures in the translation process (unpublished results). (c) 2005 Elsevier B.V. All rights reserved.

Molecular cloning of growth hormone receptor (GHR) from common carp (Cyprinus carpio L.) and identification of its two forms of mRNA transcripts

The cDNA of growth hormone receptor (GHR) was cloned from the liver of 2-year common carp (Cyprinus carpio L.) by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE). Its open reading frame (ORF) of 1806 nucleotides is translated into a putative peptide of 602 amino acids, including an extracellular ligand-binding domain of 244 amino acids (aa), a single transmembrane domain of 24 aa and an intracellular signal-transduction domain of 334 aa. Sequence analysis indicated that common carp GHR is highly homologous to goldfish (Carassius auratus) GHR at both gene and protein levels. Using a pair of gene-specific primers, a GHR fragment was amplified from the cDNA of 2-year common carp, a 224 bp product was identified in liver and a 321 bp product in other tissues. The sequencing of the products and the partial genomic DNA indicated that the difference in product size was the result of a 97 bp intron that alternatively spliced. In addition, the 321 bp fragment could be amplified from all the tissues of 4-month common carp including liver, demonstrating the occurrence of the alternative splicing of this intron during the development of common carp. Moreover, a semi-quantitative RT-PCR was performed to analyze the expression level of GHR in tissues of 2-year common carp and 4-month common carp. The result revealed that in the tissues of gill, thymus and brain, the expression level of GHR in 2-year common carp was significantly tower than that of 4-month common carp.

Genetic variation analysis within and among six varieties of common carp (Cyprinus carpio L.) in china using microsatellite markers

Five microsatellites were used to study the genetic diversity and genetic structure of one wild and five domestic varieties of common carp in China (the Yangtze River wild common carp, Xingguo red carp, purse red carp, Qingtian carp, Russian scattered scaled mirror carp and Japanese decorative carp). All loci in this study showed marked polymorphism with the number of alleles ranging from 4 to 13. Domestic varieties (except Xingguo red carp) showed less genetic diversity than the Yangtze River wild common carp in terms of allelic diversity. Population differentiation was assessed and each combination of populations displayed significant differentiation (P < 0.05) with the exception of that between the Yangtze River wild common carp and Xingguo red carp. Genetic distance analysis (Nei's standard genetic distance and pairwise F-st distance) showed that the largest distance was between Russian scattered scaled mirror carp and the Yangtze River wild common carp and the smallest distance was between the Yangtze River wild common carp and Xingguo red carp. However, among six populations Japanese decorative carp displayed the highest level of variability in terms of heterozygosity.

Two unisexual artificial polyploid clones constructed by genome addition of common carp (Cyprinus carp) and crucian carp (Carassius auratus)

A polyploid hybrid fish with natural gynogenesis can prevent segregation and maintain their hybrid vigor in their progenies. Supposing the reproduction mode of induced polyploid fish being natural gynogenesis, allopolyploid hybrid between common carp and crucian carp into allopolyploid was performed. The purpose of this paper is to describe a lineage from sexual diploid carp transforming into allotriploid and allotetraploid unisexual clones by genome addition. The diploid hybrid between common carp and crucian carp reproduces an unreduced nucleus consisting of two parental genomes. This unreduced female pronucleus will fuse with male pronucleus and form allotriploid zygote after penetration of related species sperms. Allotriploid embryos grow normally, and part of female allotriploid can produce unreduced mature ova with three genomes. Mature ova of most allotriploid females are provided with natural gynogenetic trait and their nuclei do not fuse with any entrance sperm. All female offspring are produced by gynogenesis of allotriploid egg under activation of penetrating sperms. These offspring maintain morphological traits of their allotriploid maternal and form an allotetraploid unisexual clone by gynogenetic reproduction mode. However, female nuclei of rare allotriploid female can fuse with penetrating male pronuclei and result in the appearance of allotetraploid individuals by means of genome addition. All allotetraploid females can reproduce unreduced mature eggs containing four genomes. Therefore, mature eggs of allotetraploid maintain gynogenetic trait and allotetraploid unisexual clone is produced under activation of related species sperms.