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"Clean, green and ethical" animal production. Case study: reproductive efficiency in small ruminants.

In response to changes in society and thus the marketplace, we need a vision for the future of our animal industries, including both on-farm and off-farm activities, that is "clean, green and ethical". Using small ruminants as a case study, we describe three "clean, green and ethical" strategies that farmers could use to improve reproductive performance. The first allows control of the timing of reproductive events by using socio-sexual signals (the "male effect") to induce synchronised ovulation in females. The second strategy, "focus feeding", is based on using short periods of nutritional supplements that are precisely timed and specifically designed for each event in the reproductive process (eg, gamete production, embryo survival, fetal programming, colostrum production). The third strategy aims to maximize offspring survival by a combination of management, nutrition and genetic selection for behaviour (temperament). All of these approaches involve non-pharmacological manipulation of the endogenous control systems of the animals and complement the detailed information from ultrasound that is now becoming available. Importantly, these approaches all have a solid foundation in reproductive biology. In several cases, they are currently used in commercial practice, but there is still room for improvement through both basic and applied research. Ultimately, these "clean, green and ethical" tools can be cost-effective, increase productivity and, at the same time, greatly improve the image of meat and milk industries in society and the marketplace.

Animal Husbandry↗

Protective TGFβ2/SMAD3 axis identified by TWAS in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGFβ2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGFβ signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGFβ2/SMAD3 axis in PTC.

Humans↗

Horizontally transferred cell-free chromatin particles function as autonomous 'satellite genomes' and vehicles for transposable elements within host cells.

Horizontal gene transfer (HGT) plays an important evolutionary role in prokaryotes, but it is less frequent in mammals. We previously reported that cell-free chromatin particles (cfChPs) - chromosomal fragments released from the billions of dying cells that circulate in human blood - are horizontally transferred to healthy cells with biological effects. However, the underlying mechanism and function of these effects remained unclear. We treated NIH3T3 mouse fibroblasts cells with cfChPs isolated from human serum and serially passaged the cells. The intracellular activities of cfChPs were analysed using chromatin fibre fluorography, cytogenetic analysis, immunofluorescence, and fluorescent in situ hybridisation. We discovered that the internalised cfChPs were almost exclusively comprised of non-coding DNA, and the disparate DNA sequences contained within them had randomly combined to form complex concatemers, some of which were multi-mega base pairs in size. The concatemers autonomously performed many functions attributable to the nuclear genome such as DNA, RNA and protein synthesis. They harboured human LINE-1 and Alu elements, with the potential to rearrange themselves within the mouse genome. Our results suggest that a cell simultaneously harbours two autonomous genome forms: one that is inherited (hereditary genome) and numerous others that are acquired (satellite genomes). The satellite genomes may have evolutionary functions given their ability to serve as vehicles for transposable elements and to generate a plethora of novel proteins. Our results also suggest that 'within-self' HGT may occur in mammals on a massive scale via the medium of cfChP concatemers that have undergone extensive and complex modifications resulting in their behaviour as 'foreign' genetic elements.

Chromatin↗

[Stress and allergy].

Stress is one of the components in the complex interaction of environmental, genetic, physiological, psychological, behavioural and social factors that can influence the body's ability to remain healthy or become healthy, to resist or overcome a disease. Stress can alter neuroendocrine and immune mechanisms of health and disease through various psychosocial processes. In addition, it can affect health through the impact on health-impairing behaviours and on compliance with medical regimens. At the same time, the relationship between stress and health is not unidirectional but bi-directional. Current views on the relation between stress and allergy vary from the denial of any relationship that could fundamentally help in allergy treatment to the widespread opinion that psychological stress can exacerbate some skin symptoms and precipitate asthma. The role of stress in the genesis, incidence and symptomatology of allergy still remains a controversial issue since the mechanisms of that relationship are not well understood. Starting from the biopsychosocial model of disease, we introduced the Social Readjustment Rating Scale which measures stressful life events, and the WHOQOL-BREF which measures subjective quality of life, into an extensive multidisciplinary study of immunotoxic effects of indoor bioaerosols and lifestyle. This paper describes the characteristics of those two questionnaires and discusses the relationship between stress and various domains of the quality of life. The Social Readjustment Rating Scale proved to be a reliable predictor for quality of life in the domains of physical health and environment. Future analyses will examine the role of stress and subjective quality of life in allergy.

Adult↗

Biochemical changes of mevalonate pathway in human colorectal cancer.

BACKGROUND: Alterations in the mevalonate pathway may contribute to malignant cell growth. There are differences in the aetiology, clinical behaviour, pathological and genetic features in cancer of the right versus the left colon. Here, 3-hydroxy-3-methylglutatyl coenzyme A (HMG-CoA) reductase, farnesylpyrophosphate (FPP) synthase and farnesyltransferase (Ftase) activities were measured in human colorectal cancer (CRC) and normal mucosa in order to evaluate their role as potential markers of malignancy, also in relation to cancer location. PATIENTS AND METHODS: HMG-CoA reductase, FPP synthase and Ftase activities were determined in CRC and normal mucosa of 90 patients by radiochemical assay. RESULTS: The enzymatic activities were higher in cancer than in normal mucosa. The tumours located at the left side showed higher HMG-CoA reductase activity, whereas the right side tumours showed higher levels of Ftase and FPP synthase activity. CONCLUSION: The determination of mevalonate pathway enzymes in relation to CRC location may be clinically relevant in designing anticancer targeted therapies.

Aged↗

[Epidemiology of obesity].

Overweight and obesity are conditions characterized by weight levels higher than the normal limits for age, sex, and height. Because people stratified for sex and age vary in stature and this influences weight, criteria for being overweight must take height into account: this is defined and set out in WHO guidelines on the basis of Body Mass Index (BMI): weight (kg)/height2 (m2). Obese and overweight individuals are at a greater risk of developing chronic metabolic conditions and general ill health, than those whose weights are within the recommended guidelines. Besides these chronic related conditions for which obesity is a major risk factor incur enormous expenditure. The health hazards of obesity are compounded by the influence of central fat distribution. The disease associations of central fat are present even in people who are not overweight. Waist circumference is a simple measure that gives a very reasonable estimate of the amount of central fat. Data collected in the USA and Europe show a common trend: the increase of obesity and overweight among the adult and children population. Obesity appears to be the result of several factors that interact among them such as: genetic, environment, and behaviour. Current strategies, such as reducing food intake, seem to lead to poor long term outcomes. Management has tended to neglect the unavoidable need to consider obese subjects as chronically ill patients, requiring continuous assistance for active steps to maintain weight loss. Treatments should be multidisciplinary aiming at the achievement of radical changes in the individual's lifestyle. The planning and management of preventive programs for young people such as pubertal children have been disregarded up to now. They require not only attention, but also organization, clear goals and standardized methods. Moreover, a correct education is a key-element of these issues. Our unit has designed for this purpose an observational study aimed to reach a better comprehension of the proportion of ''weight problems'' and eating behavioural patterns in a population of adolescents.

English Abstract↗

[Immunoglobulin D--new insights into its structure and function].

The IgD is unique with regard to its structure, differences between species, genetic organization and behaviour in the immune response. With the successful analysis of the structure a new picture of the function has been emerged. The function of the membrane-bound IgD as a trigger receptor of B cells is qualitatively different from the mIgM. The secreted form could act as an intercellular messenger in the network regulation of the immune response. The mechanisms of the induction and maintenance of the immunological memory and tolerance remain unclear.

B-Lymphocytes↗

[Large-cell anaplastic lymphomas: a genetic and immunophenotypic study].

PURPOSE: To characterize from a genetic point of view a group of non-Hodgkin's anaplastic large-cell lymphomas (ALCL) by Southern blot and PCR methods with different probes (molecular study) and with direct or post 24-78 hours cultures with GTC banding techniques (cytogenetic). To correlate the results to the immunophenotype performed with a complete panel of monoclonal antibodies (MoAb) according to avidin-biotine and alkaline phosphatase (APAAP) methods. MATERIAL AND METHODS: Sixty cases of ALCL were reviewed and only 19 selected (with frozen or fresh material) because a complete immunohistologic and genotypic correlation had been done. According to CD15 expression two groups were considered, CD15+ (the so-called Hodgkin's related or Hodgkin's like) and CD15- or classical type. RESULTS: Only 26.5% of cases showed immuno -genotypic correlation. Immunohistochemistry is an accurate method for activation, proliferation and B-cell nature, but T-cell cases were not stained because T-cell paraffin markers are not completely specific. CD15 group had only 30% rearranged cases with scarce cytogenetic abnormalities, as it occurs in Hodgkin's disease (HD). ALCL classical type showed 66% rearranged cases, and one of the T-cell cases showed an incomplete t (2:5) translocation or polyploid cell lines. CONCLUSIONS: Both groups have different genetic and immunophenotypic behaviour which resembles HD or NHL. CD15 positive cases or ALCL HD-related constitute a borderline entity which has to be recognized because of the different therapy and clinical behaviour.

Hodgkin Disease↗

Is there a dissociation between emotional feelings and emotional signs in autism?

There is evidence that autistic persons are deficient both in the expression and recognition of emotion. Emotions are viewed here as in part genetically determined, inborn behaviours with great importance for social regulations. Both in phylogenetic and in ontogenetic development there is a transgression from emotion-bound or signal-reflex-like behaviour chains towards an experience-based coupling of emotional signals with events lying outside emotional exchanges. We conjecture that in childhood autism there is a deficit in linking biologically based emotional signals to emotional experiences and/or a deficit in linking these signals to a third element. Mesocortical areas with close connections to the limbic systems appear to be involved.

Adolescent↗

Present state of research on ticks (Ixodoidea) in the Czech Republic.

Tick research in the Czech Republic started developing rapidly after World War II and was directed to the faunistics and taxonomy, biology, ecology and behaviour, physiology and genetics, disease transmission, host-parasite relationships and control. Altogether 15 tick species were reported from the territory of the Czech Republic. Most studies in biology, ecology and virus transmission were dedicated to Ixodes ricinus, but biology and ecology of Dermacentor reticulatus, I. laguri and I. hexagonus were also studied. Many studies were done on argasid ticks, mostly on pheromonal communication of Argas persicus and immunology of feeding of A. polonicus. Population variability of both these species was also studied. The present research on ticks is mostly directed to study of interaction among hosts, ticks and pathogens on the humoral, cellular and molecular level.

Adaptation, Physiological↗

Genetic change in actinic keratoses.

Actinic keratoses (AKs) are small scaly red areas of skin characterised histologically by dysplasia, a minority of which are thought to be precursors of squamous cell carcinoma (SCC), and which show a high frequency of regression. Surprisingly, in view of their benign clinical course, they show a high frequency of loss of heterozygosity (LOH) with a median loss of four loci with almost 20% of lesions showing loss of eight or more alleles, as well as frequent p53 mutation. Loss was common on 3p (31%), 9p (39%), 9q (22%), 13q (52%), 17p (64%) and 17q (46%), and allele loss correlated with dysplasia. Topological disturbance of p21WAF1/CIP1 expression correlated with allele loss but was also seen together with increased wild-type p53 expression and an increase in the fraction of cycling cells in the absence of allele loss or p53 mutation, and is likely to represent an early change. P21WAF1/CIP1 expression appeared independent of p53 status. The frequency of LOH in AKs exceeded that of (invasive) SCCs suggesting that the relation between the accumulation of genetic change and behaviour for non-melanoma skin cancer is not straightforward.

Alleles↗

[Modulation of behavior of mice of different genotypes by serotonin antibodies].

The effect of active immunization with conjugated serotonin-protein on the "open-field" behaviour and passive avoidance conditioning was studied in genetically different mice strains (C57BL/6 and BALB/c). The obtained immunophysiological effects of serotonin antibodies depended on genetically determined characteristics of animal behaviour. Serotonin antibodies altered rearing and crossings of the "open-field" center and retention of passive avoidance learning in C57BL/6 mice. The active immunization with conjugated serotonin-protein of BALB/c mice resulted in modulation of the "open-field" latency and both training and testing of passive avoidance behaviour.

Animals↗

Male affiliation, cooperation and kinship in wild chimpanzees.

Long-term field research has revealed that male chimpanzees, Pan troglodytes, affiliate and cooperate in several contexts. Assuming close genetic relationship among males, affiliative and cooperative behaviour have been hypothesized to evolve through the indirect effects of kin selection. We tested the hypothesis that matrilineal genetic relatedness affects patterns of male social affiliation and cooperation in an unusually large community of chimpanzees at the Ngogo study site, Kibale National Park, Uganda. Field observations indicated that six behavioural measures of affiliation and cooperation among 23 adult males were significantly correlated with each other. Sequences of the first hypervariable portion of the mtDNA genome revealed that three pairs of males and one quintet shared mtDNA haplotypes. Matrix permutation tests using behavioural and genetic data showed that males that affiliated and cooperated with each other were not closely related through the maternal line. These findings add to a growing body of empirical evidence that suggest kinship plays an ancillary role in structuring patterns of wild chimpanzee behaviour within social groups. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

Behavioural differences between individuals and two populations of stickleback (Gasterosteus aculeatus).

Behavioural syndromes are correlations between behaviours in different functional contexts. Behavioural syndromes are attracting the attention of evolutionary biologists because they mean that different behaviours might not be free to evolve independently of one another. In a landmark study, Huntingford (1976) showed that individual stickleback which were bold toward predators were also aggressive toward conspecifics and active in an unfamiliar environment. Here, I revisited the activity-aggression-boldness syndrome in stickleback and tested the hypothesis that correlations between behaviours might act as evolutionary constraints. I measured a suite of behaviours on wild-caught individuals and their offspring from two different populations and calculated heritabilities and genetic correlations between the different behaviours. I found that these behaviours were phenotypically and genetically correlated in one population but not another. On average, boldness and aggression were negatively related to each other across the populations. These results suggest that behavioural syndromes don't always act as evolutionary constraints.

Aggression↗

Variation in reproductive behaviour within a sex: neural systems and endocrine activation.

Intrasexual variation in reproductive behaviour, morphology and physiology is taxonomically widespread in vertebrates, and is as biologically and ecologically significant as the differences between the sexes. In this review, we examine the diverse patterns of intrasexual variation in reproductive behaviours within vertebrates. By illustrating the genetic, cellular, hormonal and/or neural mechanisms underlying behavioural variation in a number of species, another level of complexity is added to studies of brain organization and function. Such information increases our understanding of the unique and conserved mechanisms underlying sex and individual differences in behaviour in vertebrates as a whole. Here, we show that intrasexual variation in behaviour may be discrete or continuous in nature. Moreover, this variation may be due to polymorphism at a single genetic locus or many loci, or may even be the result of phenotypic plasticity. Phenotypic plasticity simply refers to cases where a single genotype (or individual) can produce (or display) different phenotypes. Defined in this way, plasticity subsumes many different types of behavioural variation. For example, some behavioural phenotypes are established by environmental factors during early ontogeny, others are the result of developmental transitions from one phenotype early in life to another later in life, and still other strategies are facultative with different behaviours displayed in different social contexts.

Animals↗

Inter and intra-population variation in shoaling and boldness in the zebrafish (Danio rerio).

Population differences in anti-predator behaviour have been demonstrated in several species, although less is known about the genetic basis of these traits. To determine the extent of genetic differences in boldness (defined as exploration of a novel object) and shoaling within and between zebrafish (Danio rerio) populations, and to examine the genetic basis of shoaling behaviour in general, we carried out a study that involved laboratory-raised fish derived from four wild-caught populations. Controlling for differences in rearing environment, significant inter-population differences were found in boldness but not shoaling. A larger shoaling experiment was also performed using one of the populations as the basis of a North Carolina type II breeding design (174 fish in total) to estimate heritability of shoaling tendency. A narrow-sense heritability estimate of 0.40 was obtained, with no apparent dominance effects.

Animals↗

Behavioural factors in accidents at road junctions: the use of a genetic algorithm to extract descriptive rules from police case files.

In-depth studies of behavioural factors in road accidents using conventional methods are often inconclusive and costly. To explore an alternative approach, 200 cross-flow junction road accidents were sampled from the files of Nottinghamshire Constabulary, England, coded for computer analysis using a specially devised 'Traffic Related Action Analysis Language', and then examined using a genetic algorithm (or 'rule-finder' program). For comparison, the same analyses were carried out on 100 descriptions of safe turns, and 100 of hypothetical accident descriptions provided by experienced drivers. A number of findings emerged, distinguishing between accidents turning onto and off major roads; those of younger and older drivers; those that resulted in injury or in damage only; and so on. The study suggests that multiple case-studies based on police case files could be very promising, provided homogeneous samples of accidents are used. Genetic algorithms could play a useful role in preliminary assessment, but an 'information bottleneck' remains to be overcome in capturing enough detail from each case for analysis.

Accidents, Traffic↗

Microsatellite analyses reveal fine-scale genetic structure in grey mouse lemurs (Microcebus murinus).

Information on genetic structure can be used to complement direct inferences on social systems and behaviour. We studied the genetic structure of the solitary grey mouse lemur (Microcebus murinus), a small, nocturnal primate endemic to western Madagascar, with the aim of getting further insight on its breeding structure. Tissue samples from 167 grey mouse lemurs in an area covering 12.3 km2 in Kirindy Forest were obtained from trapping. The capture data indicated a noncontinuous distribution of individuals in the study area. Using 10 microsatellite markers, significant genetic differentiation in the study area was demonstrated and dispersal was found to be significantly male biased. Furthermore, we observed an overall excess of homozygotes in the total population (F(IT) = 0.131), which we interpret as caused by fine-scale structure with breeding occurring in small units. Evidence for a clumped distribution of identical homozygotes was found, supporting the notion that dispersal distance for breeding was shorter than that for foraging, i.e. the breeding neighbourhood size is smaller than the foraging neighbourhood size. In conclusion, we found a more complex population structure than what has been previously reported in studies performed on smaller spatial scales. The noncontinuous distribution of individuals and the effects of social variables on the genetic structure have implications for the interpretation of social organization and the planning of conservation activities that may apply to other solitary and endangered mammals as well.

Animals↗