Iron and copper in progressive demyelination – New lessons from Skogholt's disease

The pathophysiological mechanisms of progressive demyelinating disorders including multiple sclerosis are incompletely understood. Increasing evidence indicates a role for trace metals in the progression of several neurodegenerative disorders. The study of Skogholt disease, a recently discovered demyelinating disease affecting both the central and peripheral nervous system, might shed some light on the mechanisms underlying demyelination. Cerebrospinal fluid iron and copper concentrations are about four times higher in Skogholt patients than in controls. The transit into cerebrospinal fluid of these elements from blood probably occurs in protein bound form. We hypothesize that exchangeable fractions of iron and copper are further transferred from cerebrospinal fluid into myelin, thereby contributing to the pathogenesis of demyelination. Free or weakly bound iron and copper ions may exert their toxic action on myelin by catalyzing production of oxygen radicals. Similarities to demyelinating processes in multiple sclerosis and other myelinopathies are discussed.     

Assessment of vulnerability to climate change using a multi-criteria outranking approach with application to heat stress in Sydney

Climate change vulnerability assessment is a complex form of risk assessment which accounts for both geophysical and socio-economic components of risk. In indicator-based vulnerability assessment (IBVA), indicators are used to rank the vulnerabilities of socio-ecological systems (SESs). The predominant aggregation approach in the literature, sometimes based on multi-attribute utility theory (MAUT), typically builds a global-scale, utility function based on weighted summation, to generate rankings. However, the corresponding requirement for additive independence and complete knowledge of system interactions by analyst are rarely if ever satisfied in IBVA.We build an analogy between the structures of Multi-Criteria Decision Analysis (MCDA) and IBVA problems and show that a set of techniques called Outranking Methods, developed in MCDA to deal with criteria incommensurability, data uncertainty and preference imprecision, offer IBVA a sound alternative to additive or multiplicative aggregation. We reformulate IBVA problems within an outranking framework, define thresholds of difference and use an outranking method, ELECTRE III, to assess the relative vulnerability to heat stress of 15 local government areas in metropolitan Sydney. We find that the ranking outcomes are robust and argue that an outranking approach is better suited for assessments characterized by a mix of qualitative, semi-quantitative and quantitative indicators, threshold effects and uncertainties about the exact relationships between indicators and vulnerability.     

Monitoring clinical trials with multiple arms

In order to benefit from the substantial overhead expenses of a large group sequential clinical trial, the simultaneous investigation of several competing treatments becomes more popular. If at some interim analysis any treatment arm reveals itself to be inferior to any other treatment under investigation, this inferior arm may be or may even need to be dropped for ethical and/or economic reasons. Recently proposed methods for monitoring and analysis of group sequential clinical trials with multiple treatment arms are compared and discussed. The main focus of the article is on the application and extension of (adaptive) closed testing procedures in the group sequential setting that strongly control the familywise error rate. A numerical example is given for illustration.     

Are “multiple cross-multiple pollen hybrids’ an answer for productive populations in Brassica campestris var. ‘brown sarson’?

Summary A set of complex crosses with multiple crosses as female parents were made using multiple pollen in turnip rape (Brassica campestris L.). These multiple cross — multiple pollen hybrids (mucromphs) were evaluated for a large number of quantitative characters including yield. New methods were proposed to study such genetic material in depth so as to formulate suitable strategies to breed for attractive seed yield.Part of the Ph. D. Thesis of junior author submitted to Indian Agricultural Research Institute, New Delhi     

Isolation and introgression in the Intermountain West: contrasting gene genealogies reveal the complex biogeographic history of the American pika (Ochotona princeps)

Aim We studied the history of colonization, diversification and introgression among major phylogroups in the American pika, Ochotona princeps (Lagomorpha), using comparative and statistical phylogeographic methods. Our goal was to understand how Pleistocene climatic fluctuations have shaped the distribution of diversity at mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) loci in this alpine specialist. Location North America’s Intermountain West. Methods We accumulated mtDNA sequence data (c. 560–1700 bp) from 232 pikas representing 64 localities, and sequenced two nuclear introns (mast cell growth factor, c. 550 bp, n = 148; protein kinase C iota, c. 660 bp, n = 139) from a subset of individuals. To determine the distribution of major mtDNA lineages, we conducted a phylogenetic analysis on the mtDNA sequence data, and we calculated divergence times among the lineages using a Bayesian Markov chain Monte Carlo approach. Relationships among nuclear alleles were explored with minimum spanning networks. Finally, we conducted coalescent simulations of alternative models of population history to test for congruence between nDNA and mtDNA responses to Pleistocene glacial cycles. Results We found that: (1) all individuals could be assigned to one of five allopatric mtDNA lineages; (2) lineages are associated with separate mountain provinces; (3) lineages originated from at least two rounds of differentiation; (4) nDNA and mtDNA markers exhibited overall phylogeographic congruence; and (5) introgression among phylogroups has occurred at nuclear loci since their initial isolation. Main conclusions Pika populations associated with different mountain systems have followed separate but not completely independent evolutionary trajectories through multiple glacial cycles. Range expansion associated with climate cooling (i.e. glaciations) promoted genetic admixture among populations within mountain ranges. It also permitted periodic contact and introgression between phylogroups associated with different mountain systems, the record of which is retained at nDNA but not mtDNA loci. Evidence for different histories at nuclear and mtDNA loci (i.e. periodic introgression versus deep isolation, respectively) emphasizes the importance of multilocus perspectives for reconstructing complete population histories.     

RIFLE标准在高容量血液滤过治疗MODS患者疗效的评价

目的：探讨不同肾功能损害时期行高容量血液滤过（HVHF）治疗对多器官功能障碍综合征（MODS）疗效的影响。方法：采用RIFLE标准,将入选的MODS患者按急性肾损伤（AKI）分为AKIⅠ期（A组）、AKIⅡ期（B组）、AKIⅢ期（C组）,以不同AKl分期作为HYI-IF治疗的时机,对比分析不同时期行HVHF治疗MODS患者的死亡率、平均重症监护病房0CU）住院时间（T1）、平均机械通气时间（T2）、平均连续血液滤过治疗时间（T3）,并将HVHF治疗前和治疗24h后的APACHEⅡ评分、SOFA评分、血浆白介素-6（IL-6）、氧合指数、血浆肌酐（Cr）、平均动脉压-（MAP）等结果进行比较。结果：1、AKIⅢ期患者死亡率显著高于AKIⅠ期和AKIⅡ期患者（P〈0．01）;AKIⅡ期患者T1、T2和T3显著高于AKIⅠ期患者（P〈0．01）;2、与AKIⅠ期和AKIⅡ期患者比较,AKIⅢ期患者HVHF治疗前APACHEⅡ评分、SOFA评分、IL-6和Cr均显著增高（P〈0．05）;AKIⅡ期患者HVHF治疗前血浆IL-6显著高于AKIⅠ期患者（P〈0．01）;3、与HVHF治疗前比较,三组患者HVHF治疗24h后IL-6、氧合指数、cr和MAP均显著改善（P〈0．01）：AKIⅢ期患者治疗后的IL-6仍显著高于AKIⅠ期和AKIⅡ期患者;AKIⅠ期和AKIⅡ期患者HVHF治疗24h后APACHEⅡ评分SOFA评分显著降低（P〈0．01）,AKIⅢ期患者治疗前后APACHEⅡ评分和SOFA评分变化无显著统计学差异。结论：RIFLE标准及IL-6对判断预后有指导意义;AKIⅠ期和Ⅱ期行HVHF可明显改善MODS的预后,而AKIⅠ期行HVHF的疗效更好。     

Fluorescence in situ hybridization with multiple repeated DNA probes applied to the analysis of wheat-rye chromosome pairing

 Fluorescence in situ hybridization (FISH) with multiple probes has been applied to meiotic chromosome spreads derived from ph1b common wheat x rye hybrid plants. The probes used included pSc74 and pSc 119.2 from rye (the latter also hybridizes on wheat, mainly B genome chromosomes), the Ae. squarrosa pAs1 probe, which hybridizes almost exclusively on D genome chromosomes, and wheat rDNA probes pTa71 and pTa794. Simultaneous and sequential FISH with a two-by-two combination of these probes allowed unequivocal identification of all of the rye (R) and most of the wheat (W) chromosomes, either unpaired or involved in pairing. Thus not only could wheat-wheat and wheat-rye associations be easily discriminated, which was already feasible by the sole use of the rye-specific pSc74 probe, but the individual pairing partners could also be identified. Of the wheat-rye pairing observed, which averaged from about 7% to 11% of the total pairing detected in six hybrid plants of the same cross combination, most involved B genome chromosomes (about 70%), and to a much lesser degree, those of the D (almost 17%) and A (14%) genomes. Rye arms 1RL and 5RL showed the highest pairing frequency (over 30%), followed by 2RL (11%) and 4RL (about 8%), with much lower values for all the other arms. 2RS and 5RS were never observed to pair in the sample analysed. Chromosome arms 1RL, 1RS, 2RL, 3RS, 4RS and 6RS were observed to be exclusively bound to wheat chromosomes of the same homoeologous group. The opposite was true for 4RL (paired with 6BS and 7BS) and 6RL (paired with 7BL). 5RL, on the other hand, paired with 4WL arms or segments of them in more than 80% of the cases and with 5WL in the remaining ones. Additional cases of pairing involving wheat chromosomes belonging to more than one homoeologous group occurred with 3RL, 7RS and 7RL. These results, while adding support to previous evidence about the existence of several translocations in the rye genome relative to that of wheat, show that FISH with multiple probes is an efficient method by which to study fundamental aspects of chromosome behaviour at meiosis, such as interspecific pairing. The type of knowledge attainable from this approach is expected to have a significant impact on both theoretical and applied research concerning wheat and related Triticeae. Received: 21 February 1996 / Accepted: 12 July 1996     

Fecundity of Euphausia lucens (Hansen) - laboratory evidence for multiple broods

There has been much controversy in the past as to how many broods euphausiids are capable of producing per season. Several authors have suggested that multiple broods are possible, although this has not been demonstrated in the laboratory. In the present study, two Euphausia lucens females were shown to spawn continuously over a period of at least 2.5 months. The euphausiids produced ≈ 33–40 broods during this period, representing 134–192% of their body carbon. Daily egg production rates varied from 0 to 86 eggs, representing a mean of 3–4% of their body carbon d⁻¹. Egg production rates were often severely depressed during moulting, and were also somewhat lower during experimental manipulation (changing food conditions). The results suggest that egg production by E. lucens, and perhaps by many other euphausiid species, are considerably higher than was previously thought.     

Enhanced shoot multiplication in Ficus religiosa L. in the presence of adenine sulphate,glutamine and phloroglucinol

Ficus religiosa (Pipal) is a long-lived valuable multipurpose forest tree. The tree is exploited because of its religious, ornamental and medicinal value and the regeneration rate in natural habitat is low. An in vitro propagation protocol has been developed from nodal segments obtained from a 45–50-year old tree. The highest bud break frequency (100 %) followed by maximum number of multiple shoots (13.9) as well as length (2.47 cm) were obtained on Woody Plant medium (WPM) supplemented with 1.0 mg/l BAP along with 0.5 mg/l IAA. Two modifications in this medium resulted in enhanced shoot regeneration-one with 200 mg/l glutamine + 150 mg/l ADS (called as MM-1) giving 32.5 shoots per nodal explant while another modification—with 200 mg/l glutamine + 150 mg/l ADS + 100 mg/l phloroglucinol (called as MM-2) giving 35.65 shoots per explant. These two media were used for sub-culturing of shoots for 4 months. The rate of shoot multiplication was same during the first three sub-cultures on MM-1 and the shoots regenerated were healthy, afterwards shoot multiplication declined. While on MM-2, shoot multiplication declined after first sub-culture and shoots underwent the problem of early leaf fall. Rooting was best induced in micro-shoots excised from proliferated shoot cultures on semi-solid as well as liquid WPM modified with 2.0 mg/l IBA and 0.5 mg/l IAA. The in vitro-raised plantlets were potted and acclimatized under culture room conditions for 25–30 days before transfer to soil conditions, where the established plants showed more than 90 % survival.     

Application of multiple response optimization design to quantum dot-encoded microsphere bioconjugates hybridization assay

The optimization of DNA hybridization for genotyping assays is a complex experimental problem that depends on multiple factors such as assay formats, fluorescent probes, target sequence, experimental conditions, and data analysis. Quantum dot-doped particle bioconjugates have been previously described as fluorescent probes to identify single nucleotide polymorphisms even though this advanced fluorescent material has shown structural instability in aqueous environments. To achieve the optimization of DNA hybridization to quantum dot-doped particle bioconjugates in suspension while maximizing the stability of the probe materials, a nonsequential optimization approach was evaluated. The design of experiment with response surface methodology and multiple optimization response was used to maximize the recovery of fluorescent probe at the end of the assay simultaneously with the optimization of target–probe binding. Hybridization efficiency was evaluated by the attachment of fluorescent oligonucleotides to the fluorescent probe through continuous flow cytometry detection. Optimal conditions were predicted with the model and tested for the identification of single nucleotide polymorphisms. The design of experiment has been shown to significantly improve biochemistry and biotechnology optimization processes. Here we demonstrate the potential of this statistical approach to facilitate the optimization of experimental protocol that involves material science and molecular biology.