Germline imprinting: battle of the sexes or battle of the X's?

The X chromosome is largely inactivated in spermatogenesis of heterogametic males, and in multiple phyla it encodes few genes specifically expressed in the male germline. Writing in Nature Genetics, Bean et al. report a parallel between male germline X inactivation in nematodes and a fungal gene-silencing mechanism that alters the way we view the evolution of both phenomena.     

Birth defects interstate data exchange: a battle worth fighting?

BACKGROUND: Regardless of where infants and children are delivered, diagnosed, or treated, an important aspect of population-based birth defects surveillance is ensuring the inclusion of children with birth defects in the catchment area. However, little is known as to how the lack of interstate birth defects data exchange affects program surveillance, monitoring, prevention, and referral activities. The study objectives were to determine the status of interstate birth defects data exchange agreements and to quantify statewide data on resident births occurring in nonresident states. METHODS: In 2004, surveys were distributed to all population-based birth defects programs in the United States to determine: 1) the types of interstate birth defects data exchange agreements that exist among birth defects programs, 2) perceived barriers in establishing exchange agreements, and 3) the extent to which out-of-state births affect a program's catchment area. The National Center for Health Statistics (NCHS) data for 2002 on live birth residency were used to determine the actual frequency of out-of-state live birth occurrence. RESULTS: Of the 52 states and territories that were surveyed, 65% (n = 34) responded. Approximately 21% (n = 7) of those that responded had an interstate data exchange agreement that allowed sharing of birth defects data with another state or a facility within another state. Approximately 53% (n = 18) of responding states indicated plans to develop an interstate birth defects data exchange agreement with other states, hospitals, or both. The NCHS data showed that the actual percentage of resident out-of-state live births ranged from 0.16 to 11.51. NCHS data also reveal that 78% of states would be able to capture >75% of their out-of-state births by sharing data on out-of-state births with the three neighboring states ranking highest in terms of such occurrences. CONCLUSIONS: Few states have interstate birth defects data exchange agreements, though all states have resident births occurring out of state. While suggestive, data beyond residency of live births are needed to quantify the degree to which the objectives of state-based birth defects programs are compromised. Resources exist to guide programs in establishing interstate data exchange agreements. Efforts to establish such agreements with only a few neighboring states could be a large step toward improving birth defects surveillance on a state, regional, and national level.     

Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting?

In classical Mendelian inheritance, each parent donates a set of chromosomes to its offspring so that maternally and paternally encoded information is expressed equally. The phenomena of X-chromosome inactivation (XCI) and autosomal imprinting in mammals violate this dogma of genetic equality. In XCI, one of the two female X chromosomes is silenced to equalize X-linked gene dosage between XX and XY individuals. In genomic imprinting, parental marks determine which of the embryo's two autosomal alleles will be expressed. Although XCI and imprinting appear distinct, molecular evidence now shows that they share a surprising number of features. Among them are cis-acting control centers, long-distance regulation and differential DNA methylation. Perhaps one of the most intriguing similarities between XCI and imprinting has been their association with noncoding and antisense RNAs. Very recent data also suggest the common involvement of histone modifications and chromatin-associated factors such as CTCF. Collectively, the evidence suggests that XCI and genomic imprinting may have a common origin. Here, I hypothesize that the need for X-linked dosage compensation was a major driving force in the evolution of genomic imprinting in mammals. I propose that imprinting was first fixed on the X chromosome for XCI and subsequently acquired by autosomes.     

Concept of immunomics: a new frontier in the battle for gene function?

At the beginning of the 21^st century, biology will try to address the function of a large number of new genes. From the perspective of technologies applied today to functional genomics, this task appears to be more complex than the effort invested in the sequencing of the human genome. Conceptually, a high-throughput approach permitting correlation between newly discovered genes and functional properties of their protein products has yet to be developed. To address relationships between tens of thousands of genes and their cognate proteins, novel interdisciplinary technologies need to emerge. In this paper, a new idea of immunomics is presented and an experimental strategy is outlined to circumvent some of the restrictions associated with methodologies currently in use. It is proposed that cloned segments of genomic DNA are used for genetic immunization to obtain a large collection of antibodies, and to generate microarrays of these antibodies for tracing differentially expressed cellular proteins.     

Epigenetics: imprinting in plants and mammals--the same but different?

Plants and animals both exhibit parental imprinting, but do they control it the same way? Recent studies show that in Arabidopsis, as in mammals, imprinted alleles are subject to DNA methylation--but, surprisingly, the default state is silence rather than activity.     

Studies of hormone evolution. Can non-hormone oligopeptides induce a functional imprinting?

Certain non-hormone oligopeptides have a greater imprinting effect on Tetrahymena than others. The imprinting potential is unrelated to the length of the peptide chain, but seems greatly dependent on the amino acid sequence. The direct growth-stimulant action developed by the peptides at the first interaction is unrelated to their imprinting effect.     

The fight against tamoxifen resistance in breast cancer therapy: a new target in the battle?

Tamoxifen is one of the most successful and widely used chemopreventive agents ever, and is an effective therapeutic agent for inhibiting growth of hormone receptor positive breast cancers. Tamoxifen and some of its metabolites bind to estrogen receptors and allow subsequent DNA binding at estrogen responsive genes, blocking some estrogenic signals while maintaining others, depending on the tissue. When used therapeutically for up to five years, cases of tamoxifen resistance appear, requiring alternative therapies. One recent proposal uniquely targets a zinc finger of the DNA binding domain of estrogen receptors, rather than the ligand binding domain, to circumvent resistance. In light of the most recent clinical data, however, it is now clear that aromatase inhibitors are the preferred first line therapy for all stages of breast cancer in post-menopausal women, whether they have had previous tamoxifen exposure or resistance.     

Genomic imprinting: A missing piece of the Multiple Sclerosis puzzle?

Evidence for parent-of-origin effects in complex diseases such as Multiple Sclerosis (MS) strongly suggests a role for epigenetic mechanisms in their pathogenesis. In this review, we describe the importance of accounting for parent-of-origin when identifying new risk variants for complex diseases and discuss how genomic imprinting, one of the best-characterized epigenetic mechanisms causing parent-of-origin effects, may impact etiology of complex diseases. While the role of imprinted genes in growth and development is well established, the contribution and molecular mechanisms underlying the impact of genomic imprinting in immune functions and inflammatory diseases are still largely unknown. Here we discuss emerging roles of imprinted genes in the regulation of inflammatory responses with a particular focus on the Dlk1 cluster that has been implicated in etiology of experimental MS-like disease and Type 1 Diabetes. Moreover, we speculate on the potential wider impact of imprinting via the action of imprinted microRNAs, which are abundantly present in the Dlk1 locus and predicted to fine-tune important immune functions. Finally, we reflect on how unrelated imprinted genes or imprinted genes together with non-imprinted genes can interact in so-called imprinted gene networks (IGN) and suggest that IGNs could partly explain observed parent-of-origin effects in complex diseases. Unveiling the mechanisms of parent-of-origin effects is therefore likely to teach us not only about the etiology of complex diseases but also about the unknown roles of this fascinating phenomenon underlying uneven genetic contribution from our parents.This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.     

Is it genomic imprinting or preferential expression?

Imprinted genes are monoallelically expressed in a parent-of-origin-specific manner, but for many genes reported to be imprinted, the occurrence of preferential expression--where both alleles are expressed but one is expressed more strongly than the other in a parent-of-origin-specific way--has been reported. This preferential expression found in genes described as imprinted has not been thoroughly addressed in genomic imprinting studies. To study this phenomenon, 50 genes, reported to be imprinted in the mouse, were chosen for investigation. Preferential expression was observed for 21 of 27 maternally expressed genes. However, only 5 of 23 paternally expressed genes showed preferential expression. Recently, it has been reported that a remarkable proportion of non-imprinted genes show differential allelic expression. If there is overlap between non-imprinted genes that are differentially expressed and imprinted genes that are preferentially expressed, we need to set new definitions of imprinted genes that, in turn, would probably lead to reassessments of the total number of imprinted genes in mammalian species.     

Genomic imprinting in mammals: an interplay between chromatin and DNA methylation?

Most imprinted loci have key regulatory elements that are methylated on only one of the parental chromosomes. For several of these 'differentially methylated regions', recent studies establish that the unmethylated chromosome has a specialized chromatin organization that is characterized by nuclease hypersensitivity. The novel data raise the question of whether specific proteins and associated chromatin features regulate the allele-specificity of DNA methylation at these imprinting control elements.     

Is The Barley Endosperm a Water Reservoir for the Embryo When Germinating Seeds Are Dried?

The water content of germinating seeds fluctuates in response to water potential changes in the surrounding environment. We tested the hypothesis that the endosperm functions as a water reservoir when imbibed seeds experience drying, and we characterized water uptake and movement within barley (Hordeum vulgare cv. Triumph) caryopses (hereafter referred to as seeds). Water movement into and through germinating barley seeds during imbibition and drying was determined gravimetrically and with the fluorescent dye trisodium 8-hydroxy-1,3,6-pyrenetrisulfonate (PTS). During imbibition, embryo tissues hydrated more rapidly and reached a higher water content (g H20/g dry weight) than did the endosperm, although the endosperm eventually contained nine times as much total water. When barley seeds that had imbibed for 12 h were exposed to moderate (-4 MPa) drying, PTS solution moved from the endosperm into the shoot meristem, radicle, and scutellum, but not vice versa. Radicle emergence and elongation proceeded for up to 8 h. With harsh (-150 MPa) drying, PTS concentrated almost exclusively in the radicle. These data illustrate that the endosperm is at least a temporary water storage compartment external to the embryo itself. We speculate that water supplied by the endosperm may be important in reducing the harmful effects of drying during the critical transition period when a germinating seed changes from a desiccation-tolerant to a desiccation-intolerant organism.     

COVID-19 therapy: What weapons do we bring into battle?

Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.     

Genomic imprinting and kinship in the social Hymenoptera: what are the predictions?

The kinship theory of genomic imprinting predicts that conflicts of interest between parents can promote the evolution of opposed expression patterns of maternally and paternally derived alleles in the offspring. The social Hymenoptera (ants, some bees, and some wasps) are particularly suitable to test this theory, because a variety of social conflicts are predicted due to relatedness asymmetries between female and male nestmates that are a corollary of haplo-diploid sex determination. Here I argue that the kin-selection predictions for genomic imprinting in social Hymenoptera might in many cases be more complex than previously suggested, because the optimal strategy will have to take fitness effects in different castes and sexes into account.     

Malnutrition and child mortality: are socioeconomic factors important?

The influences of household economic condition, maternal education, sex, and nutritional status of children on mortality were examined using multivariate analytical techniques. Weights of around 1700 children aged 2 60 months in five villages of Matlab, Bangladesh, were taken during the first half of 1981. The children were followed for 18 months and their survival was recorded. The severely malnourished children had a risk of death nine times that of their counterparts with better nutritional status. Female children had a higher risk of death than the males. Mother's education and economic condition of household also showed negative relationships with the risk of death, but the effect of mother's education was modified by economic condition and sex of the children.     

Polygyny, reproductive success and child health in rural Ethiopia: why marry a married man?

This study examines the reproductive success of men and women in rural Ethiopia as a function of their marital status, specifically by comparing polygamously and monogamously married individuals. In line with predictions from evolutionary theory, polygamy is beneficial to male reproductive success (i.e. producing larger numbers of surviving offspring). The success of polygamously married females depends on wife rank: the first wives of polygamous husbands do better than monogamously married women and much better than second or third wives. These effects are mirrored in child nutritional status: the children of second and third wives have lower weight for height. Due to potential, largely unmeasurable differences in marriageability (quality) between individuals, it was not possible to support a model of either resource-holding polygyny combined with female choice or female coercion into unwanted marriages. First wives of polygamously married men marry at a younger age and attract a higher brideprice, suggesting that both the males and females in the marriage are likely to be of higher quality (due to wealth, family status or some other factor such as beauty). Unions that end up monogamous are likely to be between slightly lower quality individuals; and second and third wives, who marry at the oldest ages and attract the lowest brideprice, may be 'making the best of a bad job'. The relatively long gap between first and second marriages may mean that first wives of highly marriageable males can enjoy considerable reproductive success before their husbands marry again.     

Are stunted child – overweight mother pairs a real defined entity or a statistical artifact?

In a methodological contribution, Dieffenbach & Stein (DS) (The Journal of Nutrition, 142(4), 771–773.) concluded that the double burden of malnutrition (DBM), represented by stunted child – overweight mother pairs (SCOM), is a statistical artifact, meaning that SCOM does not describe a unique phenomenon because the observed rates of SCOM across a number of countries were not strongly different from the product of observed rates of maternal overweight (OM) and child stunting (SC), which DS referred to as the expected rate of SCOM. However, a growing literature continues to use SCOM as an indicator of the DBM. This study shows that the analysis by DS is not sufficient to conclude that SCOM can be explained by the co-occurrence of OM and SC due to chance alone because the analysis by DS was conducted at the country level, but applied to SCOM, which is a household-level variable. Using Demographic and Health Surveys data from 202 country-year data sets, we do not confirm important implicit assumptions that are required for the claim by DS to be supported. We also outline that comparing the expected to the observed rate of SCOM is primarily informative when putting it in relation to factors that influence the supply and demand of food consumed by households. When considering these factors, we find further evidence that it is misleading to consider SCOM as a statistical artifact, as the difference between the observed and the expected rate of SCOM significantly differs by household wealth. Recognizing that SCOM is a distinct phenomenon is important for policymakers who develop double-duty strategies that address malnutrition, and for researchers who need useful indicators to study the determinants of malnutrition at the household level.     

Language learning: How much evidence does a child need in order to learn to speak grammatically?

In order to learn grammar from a finite amount of evidence, children must begin with in-built expectations of what is grammatical. They clearly are not born, however, with fully developed grammars. Thus early language development involves refinement of the grammar hypothesis until a target grammar is learnt. Here we address the question of how much evidence is required for this refinement process, by considering two standard learning algorithms and a third algorithm which is presumably as efficient as a child for some value of its memory capacity. We reformulate this algorithm in the context of Chomsky’s ‘principles and parameters’ and show that it is possible to bound the amount of evidence required to almost certainly speak almost grammatically.