Parent-of-origin specific QTL--a possibility towards understanding reciprocal effects in chicken and the origin of imprinting

Reciprocal effects for sexual maturity, egg production, egg quality traits and viability are well known in poultry crosses. They have been used in an optimal way to form profitable production hybrids. These effects have been hypothesized to originate from sex-linked genes, maternal effects or a combination of both. However, these may not be the only explanations for reciprocal effects. Recent mapping of quantitative trait loci (QTL) has revealed autosomal areas with parent-of-origin specific effects in the chicken. In mammals, parental imprinting, i.e. the specifically regulated expression of either maternal or paternal allele in the offspring, is the main cause of such effects. The most commonly accepted hypothesis for the origin of imprinting, the conflict hypothesis, assumes a genetic conflict of interest between the maternal and paternal genomes regarding the allocation of resources to the offspring. It also intrinsically implies that imprinting should not occur in oviparous taxa. However, new molecular genetic information has raised a need to review the possible involvement of imprinting or some related phenomena as a putative cause of reciprocal effects in poultry. Comparative mapping provides strong evidence for the conservation of orthologous imprinted gene clusters on chicken macrochromosomes. Furthermore, these gene clusters exhibit asynchronous DNA replication, an epigenetic mark specific for all imprinted regions. It has been proposed that these intrinsic chromosomal properties have been important for the evolution of imprinted gene expression in the mammalian lineage. Many of the mapped parent-of-origin specific QTL effects in chicken locate in or close to these conserved regions that show some of the basic features involved in monoallelic expression. If monoallelic expression in these regions would be observed in birds, the actual mechanism and cause may be different from the imprinting that evolved later in the mammalian lineage. In this review we discuss recent molecular genetic results that may provide tools for understanding of reciprocal differences in poultry breeding and the evolution of imprinting.     

The evolutionary origin and elaboration of sociality in the aculeate Hymenoptera: maternal effects, sib-social effects, and heterochrony

We discuss the evolutionary origin and elaboration of sociality using an indirect genetic effects perspective. Indirect genetic effects models simultaneously consider zygotic genes, genes expressed in social partners (especially mothers and siblings), and the interactions between them. Incorporation of these diverse genetic effects should lead to more realistic models of social evolution. We first review haplodiploidy as a factor that promotes the evolution of eusociality. Social insect biologists have doubted the importance of relatedness asymmetry caused by haplodiploidy and focused on other predisposing factors such as maternal care. However; indirect effects theory shows that maternal care evolves more readily in haplodiploids, especially with inbreeding and despite multiple mating. Because extended maternal care is believed to be a precondition for the evolution of eusociality, the evolutionary bias towards maternal care in haplodiploids may result in a further bias towards eusociality in these groups. Next, we compare kin selection and parental manipulation and then briefly review additional hypotheses for the evolutionary origin of eusociality. We present a verbal model for the evolutionary origin and elaboration of sib-social care from maternal care based on the modification of the timing of expression of maternal care behaviors. Specifically, heterochrony genes cause maternal care behaviors to be expressed prereproductively towards siblings instead of postreproductively towards offspring. Our review demonstrates that both maternal effect genes (expressed in a parental manipulation manner) and direct effect zygotic genes (expressed in an offspring control manner) are likely involved in the evolution of eusociality. We conclude by describing theoretical and empirical advances with indirect genetic effects and sociogenomics, and we provide specific quantitative genetic and genomic predictions from our heterochrony model for the evolutionary origin and elaboration of eusociality.     

Problems with retrogasserian glycerol in the treatment of trigeminal neuralgia

Following glycerol injections for trigeminal neuralgia. H?kanson, Lunsford, Apfelbaum, Beck and Lobosky and Dieckmann, among others, report that few patients have sensory loss and dysesthesia and a high percentage have sustained gratifying relief. Such was not our experience or that of Laitinen, Price, Siegfried, or Takusagawa, among others. Our own disappointing results re initial failures to achieve relief, significant sensory loss including corneal anesthesia and some dysesthesias in 77 patients are described.     

Abnormal physiology of the dorsal horn as related to the deafferentation syndrome

The spinal cord dorsal horn has been implicated in the generation of pain and dysesthesias following nerve and nerve root damage and/or avulsion, as well as following damage in adjacent spinal cord regions. Alterations in the functional properties of dorsal horn neurons occur after deafferentation and may underlie the occurrence of abnormal sensations referred to the denervated body part. Abnormal activity following deafferentation has also been noted at thalamic and cortical levels. Some of these post-denervation functional changes, determined anatomically and/or electrophysiologically, are reviewed as well as the results of behavioral studies of the deafferentation syndrome in the rat.     

A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes

Diabetes mellitus is a multifactorial global health disorder that is rising at an alarming rate. Cardiovascular diseases, kidney damage and neuropathy are the main cause of high mortality rates among individuals with diabetes. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes is to target alpha-amylase and alpha-glucosidase, enzymes that catalyzes starch hydrolysis in the intestine. At present, approved inhibitors for these enzymes are restricted to acarbose, miglitol and voglibose. Although these inhibitors retard glucose absorption, undesirable gastrointestinal side effects impede their application. Therefore, research efforts continue to seek novel inhibitors with improved efficacy and minimal side effects. Natural products of plant origin have been a valuable source of therapeutic agents with lesser toxicity and side effects. The anti-diabetic potential through alpha-glucosidase inhibition of plant-derived molecules are summarized in this review. Eight molecules (Taxumariene F, Akebonoic acid, Morusin, Rhaponticin, Procyanidin A2, Alaternin, Mulberrofuran K and Psoralidin) were selected as promising drug candidates and their pharmacokinetic properties and toxicity were discussed where available.

     

Antineoplastic potential of medicinal plants

Cancer is one of the most dreaded diseases worldwide and the incidence is on the rise in both developing and developed countries. It is treated by chemotherapy, radiotherapy and surgery. In spite of advances in treatment strategies, cancer still remains a major cause of death. Research is on for development of better drugs which are more effective and simultaneously cause fewer side effects. Plants have been used for the treatment of various ailments of man and animals since ages. They are being screened extensively to explore the possibility of development of economically viable anticancer drugs. Natural products of plant origin currently constitute a considerable proportion of commercially available antineoplastic drugs. This review gives an insight into commercially available anticancer drugs of plant origin and also patents granted to plant derived components, extracts and polyherbal formulations possessing anticancer activity. The exhaustive work reviewed here on antineoplastic activity of various plants both in vitro and experimental models throughout the world will help design further research in this field.     

A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping. I. Basic theory and an analysis of alcohol dehydrogenase activity in Drosophila

Because some genes have been cloned that have a known biochemical or physiological function, genetic variation can be measured in a population at loci that may directly influence a phenotype of interest. With this measured genotype approach, specific alleles or haplotypes in the probed DNA region can be assigned phenotypic effects. In this paper we address several problems encountered in implementing the measured genotype approach with restriction site data. A number of analytical problems arise in part as a consequence of the linkage disequilibrium that is commonly encountered when dealing with small DNA regions: 1) different restriction site polymorphisms are not statistically independent, 2) the sites being measured are not likely to be the direct cause of the associated phenotypic effects, 3) haplotype classes may be phenotypically heterogeneous, and 4) the sites that are most strongly associated with phenotypic effects are not necessarily the most closely linked to the actual genetic cause of the effects. When recombination and gene conversion are rare, the primary cause of linkage disequilibrium is history (mutational origin, genetic drift, hitchhiking, etc.). We deal with historical association directly by producing a cladogram that partially reconstructs the evolutionary history of the present-day haplotype variability. The cladogram defines a nested analysis of variance that simultaneously detects phenotypic effects, localizes the effects within the cladogram, and identifies haplotypes that are potentially heterogeneous in their phenotypic associations. The power of this approach is illustrated by an analysis of the associations between alcohol dehydrogenase (ADH) activity and restriction site variability in a 13-kb fragment surrounding the ADH locus in Drosophila melanogaster.     

Combination therapy: A new strategy to manage diabetes and its complications

Diabetes mellitus is the most common metabolic disorder. The major cause of mortality and morbidity here is due to the complications caused by increased glucose concentrations. All the available commercial antidiabetic drugs are associated with side effects. The combination therapy could be a new and highly effective therapeutic strategy to manage hyperglycemia. Combination of commercial drugs with phytochemicals may reduce the side effects caused by these synthetic drugs. Herbal products have been thought to be inherently safe, because of their natural origin and traditional use rather than based on systemic studies. New formulation and cocrystallisation strategies need to be adopted to match the bioavailability of the drug and the phytochemical. This review describes in detail, the observed synergy and mechanism of action between phytochemicals and synthetic drugs in effectively combating. The mode of action of combination differs significantly than that of the drugs alone; hence isolating a single component may lose its importance thereby simplifying the task of pharma industries.     

Progress in Tetanus Prophylaxis: The Advent of Human Antitoxin

Injections of tetanus antitoxin of animal origin frequently cause serious disability and sometimes death. Despite world-wide knowledge of these effects, millions of prophylactic injections of equine tetanus antitoxin are given annually, and it is continually proposed that the dosage be increased in order to obtain higher “protective” levels in the serum, a procedure which would increase the incidence and severity of reactions. Furthermore, equine antitoxin frequently fails to prevent tetanus.Tetanus antitoxin of human origin is available which carries no risk of complications and confers a higher degree of immunity more quickly than equine antitoxin. The cost of treating reactions to horse serum, together with the financial loss incurred by work-absence, far outweighs the cost of human antitoxin. In the author''s opinion, the use, in this country, of antitoxin of animal origin is no longer medically acceptable and may well prove legally indefensible.     

Vestibulogenic imbalance.

Vestibular lesions may cause imbalance that long outlasts vertigo. Photographic analysis in five cases showed defects not only of the tilting reactions, which are of labyrinthine origin, but also of certain other postural reactions, notably the counterpoising and protective stepping reactions. All of these reflexes are unconscious and consequently such patients are rendered unstable in several ways simultaneously and may have difficulty describing their symptoms.     

Molecular evidence for transcription of genes on a B chromosome in Crepis capillaris

Dispensable, supernumerary (B) chromosomes are found in diverse eukaryotic species. The origin and genetic consequences of B chromosomes have been the subjects of speculation for more than a century. Until now, there has been no molecular evidence that B chromosome DNA is transcribed and there is no unequivocal evidence as to their origin. B chromosomes are considered to be genetically inert although they appear to cause a variety of phenotypic effects. We report that members of one of two ribosomal RNA gene families that are confined to the B chromosomes of a plant, Crepis capillaris, are transcribed--thus providing the first molecular evidence of gene activity on B chromosomes. Sequence analysis of part of the A and B chromosome rRNA genes, together with comparisons with related species, indicates that the B chromosome rRNA genes originate from the A chromosome.     

Can a Place of Origin of the Main Cystic Fibrosis Mutations Be Identified?

The genetic background of the mutations that most often cause cystic fibrosis (CF) is different from that of non-CF chromosomes in populations of European origin. It is not known whether these haplotype backgrounds could be found at high frequencies in populations in which CF is, at present, not common; such populations would be candidates for the place of origin of CF mutations. An analysis of haplotypes of CF transmembrane conductance regulator, together with their variation in specific CF chromosomes, in a worldwide survey of normal chromosomes shows (1) a very low frequency or absence of the most common CF haplotypes in all populations analyzed and (2) a strong genetic variability and divergence, among various populations, of the chromosomes that carry disease-causing mutations. The depth of the gene genealogy associated with disease-causing mutations may be greater than that of the evolutionary process that gave rise to present-day human populations. The concept of "population of origin" lacks either spatial or temporal meaning for mutations that are likely to have been present in Europeans before the ethnogenesis of present populations; subsequent population processes may have erased the traces of their geographic origin.     

What happens when Trypanosoma brucei leaves Africa

Julius Lukes and co-workers evaluated the evolutionary origin of Trypanosoma equiperdum and Trypanosoma evansi, parasites that cause horse and camel diseases. Although similar to T. brucei, the sleeping-sickness parasite, these trypanosomes do not cycle through the tsetse fly and have been able to spread beyond Africa. Transmission occurs sexually, or via blood-sucking flies or vampire bats. They concluded that these parasites, which resemble yeast petite mutants, are T. brucei sub-species, which have evolved recently through changes in mitochondrial DNA.     

Developmental consequences of autosomal aneuploidy in mammals

Autosomal aneuploidy in mammals adversely affects developmental processes. In human beings, for example, trisomy 21 is the most frequent aneuploidy detected among newborns and the most common known genetic cause of mental retardation. In this review, several hypotheses are discussed that have been proposed to explain the mechanisms by which aneuploidy (especially trisomy) disrupts development. These mechanisms included specific gene dosage effects, generalized disruption of genetic homeostasis, and the influence of the parental origin of the duplicated chromosome. The availability of specific chromosomal rearrangements in mice, coupled with selective breeding schemes, permits generation of aneuploidy of specific chromosomes or chromosomal segments on controlled genetic backgrounds, thus enabling the systematic study of the causes and consequences of defined aneuploidy. Phenotypic characteristics associated with a number of specific aneuploidies in the mouse are discussed. Emphasis is placed on the effects of trisomy 16. Genetic homology between mouse chromosome 16 and human chromosome 21 has led investigators to suggest that analogous mechanisms will be responsible for the developmental abnormalities produced in these respective aneuploidies. Analysis of trisomy 16 mice from the organismal to the subcellular level has revealed a number of phenotypic characteristics (particularly neurobiologic ones) shared with human trisomy 21. The dosage effects of shared genes (or their products) may contribute to the development of these features.     

Multiple congenital defects in a female calf: a case report

This case report describes a female calf with arthogryposis, an extra set of incision teeth, ventral abdominal hernia, tibial hemimelia and the nonunion of mullerian ducts. This is possibly the first occurrence of these anomalies in one animal. The cause of these anomalies may have been genetic in origin due to the close relationship between the dam and the sire and the negative history for such various tetragenic factors.     

Genome-wide patterns of expression in Drosophila pure species and hybrid males

One of the most fundamental questions for understanding the origin of species is why genes that function to cause fertility in a pure-species genetic background fail to produce fertility in a hybrid genetic background. A related question is why the sex that is most often sterile or inviable in hybrids is the heterogametic (usually male) sex. In this survey, we have examined the extent and nature of differences in gene expression between fertile adult males of two Drosophila species and sterile hybrid males produced from crosses between these species. Using oligonucleotide microarrays and real-time quantitative polymerase chain reaction, we have identified and confirmed that differences in gene expression exist between pure species and hybrid males, and many of these differences are quantitative rather than qualitative. Furthermore, genes that are expressed primarily or exclusively in males, including several involved in spermatogenesis, are disproportionately misexpressed in hybrids, suggesting a possible genetic cause for their sterility.     

The evolution of HIV-1 and the origin of AIDS

The major cause of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus type 1 (HIV-1). We have been using evolutionary comparisons to trace (i) the origin(s) of HIV-1 and (ii) the origin(s) of AIDS. The closest relatives of HIV-1 are simian immunodeficiency viruses (SIVs) infecting wild-living chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla gorilla gorilla) in west central Africa. Phylogenetic analyses have revealed the origins of HIV-1: chimpanzees were the original hosts of this clade of viruses; four lineages of HIV-1 have arisen by independent cross-species transmissions to humans and one or two of those transmissions may have been via gorillas. However, SIVs are primarily monkey viruses: more than 40 species of African monkeys are infected with their own, species-specific, SIV and in at least some host species, the infection seems non-pathogenic. Chimpanzees acquired from monkeys two distinct forms of SIVs that recombined to produce a virus with a unique genome structure. We have found that SIV infection causes CD4⁺ T-cell depletion and increases mortality in wild chimpanzees, and so the origin of AIDS is more ancient than the origin of HIV-1. Tracing the genetic changes that occurred as monkey viruses adapted to infect first chimpanzees and then humans may provide insights into the causes of the pathogenicity of these viruses.     

Asexuality alone does not explain the success of clonal forms in insects with geographical parthenogenesis

Asexual forms of invertebrates are relatively common. They are often more successful than their sexual progenitors. Especially in insects, the pattern called geographical parthenogenesis shows that asexuality is important in speciation and ecological adaptation. In geographical parthenogenesis the clones have a wider distribution than the sexual forms they originate from. This indicates that they have a broader niche they may utilize successfully. The cause of this apparent success is, however, hard to come by as the term asexuality covers separate phenomena that are hard to disentangle from the mode of reproduction itself. Asexual insects are often polyploid, of hybrid origin, or both and these phenomena have been argued to explain the distribution patterns better than clonality. In this study we survey the literature on arthropods with geographical parthenogenesis in an attempt to clarify what evidence there is for the different phenomena explaining the success of the clonal forms. We focus on the few species where knowledge of distribution of different ploidy levels allows for a distinction of contributions from different phenomena to be made. Our survey support that asexuality is not the only factor underlying the success of all asexuals. Evidence about the importance of a hybrid origin of the clones is found to be meagre as the origin of clones is unknown in the majority of cases. Asexuality, hybridity and polyploidy are intertwined phenomena that each and all may contribute to the success of clonal taxa. Polyploidy, however, emerges as the most parsimonious factor explaining the success of these asexual invertebrate taxa.     

Le paradoxe des fièvres prolongées inexpliquées

Fever of unknown origin are defined by a fever greater than 38.3 °C evolving during at least three weeks and without diagnosis despite appropriate explorations. Despite medical advances, they remain unexplained in 20 to 50% of cases after exhaustive explorations and the proportion is increasing in the literature. More than 200 diseases have been reported as a cause. The infectious (viral disease, tuberculosis…) and neoplastic causes (mainly lymphomas) seemed to be reduced to the benefit of noninfectious inflammatory diseases (Still's disease, giant cell arteritis…). Drug fever and factitious fever are also common. Genetic recurrent fevers form a special group, which benefit of recent advances in genetics. Diagnosis of these fevers of unknown origin is based on clinical examination and laboratory and radiologic investigation. Despite prospective protocols, it is difficult today to provide recommendations on the management and to suggest a hierarchy of tests. The role of modern explorations as FDG–PET remains to be clarified. The overall prognosis of these fevers of unknown origin remains good and the use of empirical therapeutic trials must remain exceptional.