Methylglyoxal and small heat shock proteins

Methylglyoxal is a highly reactive dicarbonyl compound formed during glucose metabolism and able to modify phospholipids, nucleic acids, and proteins belonging to the so-called dicarbonyl proteome. Small heat shock proteins participating in protection of the cell against different unfavorable conditions can be modified by methylglyoxal. The probability of methylglyoxal modification is increased in the case of distortion of glucose metabolism (diabetes), in the case of utilization of glycolysis as the main source of energy (malignancy), and/or at low rate of modified protein turnover. We have analyzed data on modification of small heat shock protein HspB1 in different tumors and under distortion of carbohydrate metabolism. Data on the effect of methylglyoxal modification on stability, chaperone-like activity, and antiapoptotic activity of HspB1 were analyzed. We discuss data on methylglyoxal modifications of lens α-crystallins. The mutual dependence and mutual effects of methylglyoxal modification and other posttranslational modifications of lens crystallins are analyzed. We conclude that although there is no doubt that the small heat shock proteins undergo methylglyoxal modification, the physiological significance of this process remains enigmatic, and new experimental approaches should be developed for understanding how this type of modification affects functioning of small heat shock proteins in the cell.     

Nutrition in the treatment of attention-deficit hyperactivity disorder: a neglected but important aspect

Attention-deficit hyperactivity disorder (ADHD) is multidetermined and complex, requiring a multifaceted treatment approach. Nutritional management is one aspect that has been relatively neglected to date. Nutritional factors such as food additives, refined sugars, food sensitivities/allergies, and fatty acid deficiencies have all been linked to ADHD. There is increasing evidence that many children with behavioral problems are sensitive to one or more food components that can negatively impact their behavior. Individual response is an important factor for determining the proper approach in treating children with ADHD. In general, diet modification plays a major role in the management of ADHD and should be considered as part of the treatment protocol.     

Assessing ancient DNA studies

The study of ancient DNA has the potential to make significant and unique contributions to ecology and evolution. However, the techniques used contain inherent problems, particularly with regards to the generation of authentic and useful data. The solution currently advocated to reduce contamination and artefactual results is to adopt criteria for authentication. Nevertheless, these criteria are not foolproof, and we believe that they have, in practice, replaced the use of thought and prudence when designing and executing ancient DNA studies. We argue here that researchers in this field must take a more cognitive and self-critical approach. Specifically, in place of checking criteria off lists, researchers must explain, in sufficient enough detail to dispel doubt, how the data were obtained, and why they should be believed to be authentic.     

An integral approach to the victims of war

Contemporary psychotherapy is of integral nature. It is a part of integral medicine and of the integral viewpoint in science. Integrity is the opposite of polarity. There can be no doubt about it, sub-specialisation deepens the insight, simultaneously narrowing the efficiency of any activity. Integration is mandatory if we are to approach the victims of the Patriotic war in Croatia. Biological, psychological, social, philosophical and religious standpoints of an individual and a group of facilitators make the appropriate form of that approach. This is why education of facilitators has been directed towards integral way of thinking.     

Can children withhold consent to treatment?

A dilemma exists when a doctor is faced with a child or young person who refuses medically indicated treatment. The Gillick case has been interpreted by many to mean that a child of sufficient age and intelligence could validly consent or refuse consent to treatment. Recent decisions of the Court of Appeal on a child''s refusal of medical treatment have clouded the issue and undermined the spirit of the Gillick decision and the Children Act 1989. It is now the case that a child patient whose competence is in doubt will be found rational if he or she accepts the proposal to treat but may be found incompetent if he or she disagrees. Practitioners are alerted to the anomalies now exhibited by the law on the issue of children''s consent and refusal. The impact of the decisions from the perspectives of medicine, ethics, and the law are examined. Practitioners should review each case of child care carefully and in cases of doubt seek legal advice.     

Perspectives in winter limnology: closing the annual cycle of freezing lakes

Winter has traditionally been considered as an ecologically insignificant season and, together with technical difficulties, this has led winter limnology to lag behind summer limnology. Recently, rapidly expanding interest in climate warming has increased water research in winter. It has also become clear that neither winter conditions of lakes nor under-ice communities are as static as often supposed. Although interannual differences in water temperature are small, close to the maximum density temperature, they may have profound effect on under-ice hydrodynamics. Thus, stochastic variations in weather, particularly those preceding the time of freezing and ice melting, may have important consequences for hydrodynamics which then affect the distributions and conditions of microorganisms and probably further to higher trophic levels. Even fish distributions can be dictated by under-ice conditions and their activities as well as behavior can sometimes approach those in summer. Life in freshwater ice is one of the least studied aspects of winter limnology and recent studies suggest that a thorough evaluation is needed. Altogether there are strengthening signs that winter should be considered as an integral part in the functioning and dynamics of lakes affecting quantitative and qualitative characteristics of aquatic communities in summer. There are great prospects that more thorough understanding of the prevailing limnological conditions in winter will improve our understanding of lake ecosystems in their entirety, and there is no doubt that such an approach requires multidisciplinary and long- term studies at different spatial scales.     

Prediction of protein signal sequences and their cleavage sites by statistical rulers

Functioning as an "address tag" or "zip code" that guides nascent proteins (newly synthesized proteins in the cytosol) to wherever they are needed, signal peptides (also called targeting signals or signal sequences) have become a crucial tool in finding new drugs or reprogramming cells for gene therapy. To effectively and timely use such a tool, however, the first important thing is to develop an automated method for quickly and accurately identifying the signal peptide for a given nascent protein. With the avalanche of new protein sequences generated in the post-genomic era, the challenge has become even more urgent and critical. In this paper, five statistical rulers were derived via performing a mutual information analysis. By combining these statistical rulers, a new prediction algorithm was established and high success prediction rates were observed. The new algorithm may play a complementary role to the existing algorithms in this area. It is anticipated that the mutual information approach introduced here may be very useful for studying many other sequence-coupling problems in molecular biology as well.     

Model Systems versus Outgroups Alternative Approaches to the Study of Head Development and Evolution

There is widespread recognition of a recent coming togetherof developmental and evolutionary biology in the study of problemsof mutual interest. Contemporary studies into the developmentand evolution of the head largely comprise two parallel approaches,or research strategies the model systems approach and the comparativeapproach. The two strategies share the same general goal—greaterunderstanding of cranial development and evolution—buttypically emphasize different problems, ask different questions,and employ different methods, reflecting the contrasting backgroundsand biases of each group of investigators, there has been relativelylittle true synthesis. Each strategy is making important andvalid contributions, but both have limitations. Resolution ofmany fundamental and long-standing problems in cranial developmentand evolution will require a combined approach that incorporatesthe technical and conceptual strengths of each discipline.     

Why we need observational studies to evaluate the effectiveness of health care.

The view is widely held that experimental methods (randomised controlled trials) are the "gold standard" for evaluation and that observational methods (cohort and case control studies) have little or no value. This ignores the limitations of randomised trials, which may prove unnecessary, inappropriate, impossible, or inadequate. Many of the problems of conducting randomised trials could often, in theory, be overcome, but the practical implications for researchers and funding bodies mean that this is often not possible. The false conflict between those who advocate randomised trials in all situations and those who believe observational data provide sufficient evidence needs to be replaced with mutual recognition of the complementary roles of the two approaches. Researchers should be united in their quest for scientific rigour in evaluation, regardless of the method used.     

A goal programming network for linear programming

Tank and Hopfield have shown that networks of analog neurons can be used to solve linear programming (LP) problems. We have re-examined their approach and found that their network model frequently computes solutions that are only suboptimal or that violate the LP problem's constraints. As their approach has proven unreliable, we have developed a new network model: the goal programming network. To this end, a network model was first developed for goal programming problems, a particular type of LP problems. From the manner the network operates on such problems, it was concluded that overconstrainedness, which is possibly present in an LP formulation, should be removed, and we have provided a simple procedure to accomplish this.     

In support of null hypothesis significance testing

Many criticisms have been levelled at null hypothesis significance testing (NHST). It is argued here that although there is reason to doubt that data subjected only to NHST have been subjected to sufficient analysis, the search for clear answers to well-formulated questions derived from substantive hypotheses is well served by NHST. To reliably draw inferences from data, however, NHST may need to be complemented by additional methods of analysis, such as the use of confidence intervals and of estimates of the degree of association between independent and dependent variables. It is argued that these should be seen as complements of, rather than as substitutes for, NHST since they do not directly test the strength of evidence against a null hypothesis.     

Cnidarian taphonomy and affinities of the Ediacara biota

Plaster impressions and sand casts of extant medusae, a chondrophoran, and a pennatulid share basic structural characteristics with fossils in the Upper Proterozoic Ediacara assemblage. Impressions of extant medusae and Proterozoic circular impressions show general similarities in arrangement and position of radial and concentric structures and a central raised boss. However, annular rings and radial grooves are more numerous in the Proterozoic fossils and strongly folded or deformed fossils are rare as compared with impressions of modem medusae. Recent pennatulids yield impressions that are more deformed and irregular than the Proterozoic genus Charniodiscus. The greater frequency of deformation of most simulated fossil medusoids relative to Precambrian circular impressions implies that Proterozoic medu-soids were substantially stiffer than many modern taxa of comparable sizes. Many fossils with abundant circular rings have no constructional counterparts among the extant forms studied here and their medusoid affinities should remain in doubt. The structural simplicity of impressions of Ediacara organisms and extant cnidarians suggests that their mutual similarities may be due to convergence. However, there is no compelling morphological reason to reject the claim that some Proterozoic fossils may share affinities with living cnidarians. □ Taphonomy. Ediacara biota, cnidarians, phylogenetic relationships.     

Resolving the iterated prisoner's dilemma: theory and reality

Pairs of unrelated individuals face a prisoner's dilemma if cooperation is the best mutual outcome, but each player does best to defect regardless of his partner's behaviour. Although mutual defection is the only evolutionarily stable strategy in one-shot games, cooperative solutions based on reciprocity can emerge in iterated games. Among the most prominent theoretical solutions are the so-called bookkeeping strategies, such as tit-for-tat, where individuals copy their partner's behaviour in the previous round. However, the lack of empirical data conforming to predicted strategies has prompted the suggestion that the iterated prisoner's dilemma (IPD) is neither a useful nor realistic basis for investigating cooperation. Here, we discuss several recent studies where authors have used the IPD framework to interpret their data. We evaluate the validity of their approach and highlight the diversity of proposed solutions. Strategies based on precise accounting are relatively uncommon, perhaps because the full set of assumptions of the IPD model are rarely satisfied. Instead, animals use a diverse array of strategies that apparently promote cooperation, despite the temptation to cheat. These include both positive and negative reciprocity, as well as long-term mutual investments based on 'friendships'. Although there are various gaps in these studies that remain to be filled, we argue that in most cases, individuals could theoretically benefit from cheating and that cooperation cannot therefore be explained with the concept of positive pseudo-reciprocity. We suggest that by incorporating empirical data into the theoretical framework, we may gain fundamental new insights into the evolution of mutual reciprocal investment in nature.     

Isolation and detection of Listeria spp, Salmonella spp and Yersinia spp using a simultaneous enrichment step followed by a surface adhesion immunofluorescent technique

There has been a proliferation of techniques and methods reported for analysis of water samples to determine the presence of the protozoan pathogens Cryptosporidium parvum and Giardia lamblia. Many of the proposed methods are presented as complete procedures, which include sampling, processing, staining, or detection steps while other methods are not complete. Some proposed methods have been extensively tested in multi-laboratory settings, however, others are still in the developmental stage. A set of evaluation criteria has been developed to evaluate the many proposed methods. These criteria have been applied as an example, to an existing method. These criteria should be useful to individuals attempting to evaluate methods developed for detecting protozoa in water, and conversely, they should serve as a guideline for individuals interested in developing methods, allowing them to gather data with and about their methods, and present this data in a manner that is both logical and easily evaluated.     

Optimal Aggregation of Binary Classifiers for Multiclass Cancer Diagnosis Using Gene Expression Profiles

Multiclass classification is one of the fundamental tasks in bioinformatics and typically arises in cancer diagnosis studies by gene expression profiling. There have been many studies of aggregating binary classifiers to construct a multiclass classifier based on one-versus-the-rest (1R), one-versus-one (11), or other coding strategies, as well as some comparison studies between them. However, the studies found that the best coding depends on each situation. Therefore, a new problem, which we call the ldquooptimal coding problem,rdquo has arisen: how can we determine which coding is the optimal one in each situation? To approach this optimal coding problem, we propose a novel framework for constructing a multiclass classifier, in which each binary classifier to be aggregated has a weight value to be optimally tuned based on the observed data. Although there is no a priori answer to the optimal coding problem, our weight tuning method can be a consistent answer to the problem. We apply this method to various classification problems including a synthesized data set and some cancer diagnosis data sets from gene expression profiling. The results demonstrate that, in most situations, our method can improve classification accuracy over simple voting heuristics and is better than or comparable to state-of-the-art multiclass predictors.     

Normalization and binning of historical and multi-source microsatellite data: overcoming the problems of allele size shift with allelogram

Microsatellite allele data have long been plagued by size shifts that can at best make it difficult to accurately assign genotypes to allele products, and at worse can cause whole batches of data from different instruments, dates or laboratories to be incorrectly assigned. Although modern genotyping technology (capillary electrophoresis) has overcome many of these problems, concern remains regarding the consistency of scores within a laboratory over time and between laboratories when combining data from multiple sources into a single analysis. There remain a large number of laboratories using older technologies or combining data from multiple sources. In addition, thousands of data sets that could potentially be expanded as samples become available are generally regarded as unusable because of the effort that would be required to validate congruence of genotypes from old and new data sets. We present methods to normalize and bin alleles from multiple data sources using a relatively small set of controls and the freely available program allelogram.     

Microscopy: an art?

There can be no doubt that the finest creator of beauty is Mother Nature. And in many ways, science is the exploration of this beauty and of the mechanisms that have created it. Microscopy, as a technique in scientific investigation, has had a key role in uncovering nature's beauty, which has led some to propose that microscopy could be described as an art or even an art form. But is this claim justified?     

Modelling larval dispersal and behaviour of coral reef fishes

Coral reef fish spend their first few weeks developing in the open ocean, where eggs and larvae appear merciless to tides and currents, before attempting to leave the pelagic zone and settle on a suitable reef. This pelagic dispersal phase is the process that determines population connectivity and allows replenishment of harvested populations across multiple coral reef habitats. Until recently this pelagic larval dispersal phase has been poorly understood and has often been referred to as the ‘black-box’ in the life-history of coral reef fishes. In this perspective article we highlight three areas where mathematical and computational approaches have been used to aid our understanding of this important ecological process. We discuss models that provide insights into the evolution of the pelagic larval phase in coral reef fish, an unresolved question which lends itself well to a modelling approach due to the difficulty in obtaining empirical data on this life history strategy. We describe how studies of fish hearing and physical sound propagation models can be used to predict the detection distance of reefs for settling larval fish, and the potential impact of anthropogenic noise. We explain how random walk models can be used to explore individual- and group-level behaviour in larval fish during the dispersal and settlement stage of their life-history. Finally, we discuss the mutual benefits that mathematical and computational approaches have brought to and gained from the field of larval behaviour and dispersal of reef fishes.     

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 5/6. Perspectives in mutation epidemiology, 6. A 1983 view of sentinel phenotypes

A sentinel phenotype is a clinical disorder or syndrome that (1) occurs sporadically as a consequence of a single, highly penetrant mutant gene, (2) is a dominant or X-linked trait of considerable frequency and low fitness, and (3) is uniformly expressed and accurately diagnosable with minimal effort at or near birth. Although 1828 autosomal dominant traits are known in human beings, 36 can be considered as candidate sentinel phenotypes, along with 5 X-linked disorders. Based on surveys of malformations in infants and children, 16 additional traits are proposed beyond previous lists. In Hungary, the 24 syndromes or defects with reliable manifestations in newborn infants occur with a frequency of 2.5-3.3 per 10 000 live births. As markers of human mutations, sentinel phenotypes have the advantage of representing germinal mutations that result in significant health problems. There are severe disadvantages that have, to date, prevented the launching of a field demonstration of the value of these phenotypes in mutation epidemiology. Agreement on a list of phenotypes has been delayed by continued recognition of two or more distinct genetic diseases within what was once thought to be a single disorder. For the same reason, most of the candidate sentinel phenotypes have not been assigned unique codes in the International Classification of Diseases. Each of the disorders is so rare and has features that overlap with so many other syndromes that highly trained clinical dysmorphologist and pediatric ophthalmologists would have to be engaged in any study. The sentinel phenotype approach, like other strategies in mutation epidemiology, would encounter problems with linkage among files of data, privacy, and access to sufficiently large populations. In contrast with the approach using multiple protein variants (as in the study of blood from offspring of survivors of the atomic bombs in Hiroshima and Nagasaki), the sentinel phenotype approach would likely be much less expensive and would encounter far fewer false attributions of paternity, but also would require a much larger study population. The best option for the present, in our opinion, is to broaden and sustain critical discussion of the approach. Perhaps the goal should be to plan a field demonstration by involving appropriate clinicians, epidemiologists, and public health officials. A pilot effort underway in Hungary may well give insight to applying the approach in a significantly larger population.