“It could just be an additional test couldn't it?” 1 Genetic testing for susceptibility to aggression and violence

Much of the current genetic research into aggressive and violent behavior focuses on young people and might appear to offer the hope of targeted prediction and intervention. In the UK data are collected on children from various agencies and collated to produce “at risk of offending” identities used to justify intervention. Information from behavioral genetic tests could conceivably be included. Regulatory frameworks for collecting, storing and using information from DNA samples differ between the health service and the police particularly in the need for consent and the treatment of children. This paper draws on discussions with professionals involved with “problem” young people to consider their views on the utility of genetic research for tackling violent/aggressive behavior and the impact an identification of genetic susceptibility might have on their clients.     

The relative importance of viral lysis and nanoflagellate grazing for prokaryote mortality in temperate lakes

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Risky individuals and the politics of genetic research into aggressiveness and violence

New genetic technologies promise to generate valuable insights into the aetiology of several psychiatric conditions, as well as a wider range of human and animal behaviours. Advances in the neurosciences and the application of new brain imaging techniques offer a way of integrating DNA analysis with studies that are looking at other biological markers of behaviour. While candidate 'genes for' certain conditions, including schizophrenia and bipolar disorders, are said to be 'un-discovered' at a faster rate than they are discovered, many studies are being conducted on personality traits such as aggressiveness and anti-social traits. The clinical applicability and implications of these studies are often discussed within the scientific community. However, little attention has so far been paid to their possible policy implications in relation to criminality management and to Criminal Law itself. Similarly, the related ethical issues arising in the field of crime control, and the tensions between enhancing security for society and protecting civil liberties, are currently under-explored. This paper investigates these ethical issues by focusing on the views of those professionals - including judges, lawyers, probation officers and social workers - who work with individuals 'deemed at risk' of violent and aggressive behaviours. It also discusses and problematizes mainstream rhetoric and arguments around the notion of 'risky individuals'.     

Identification and characterization of in vitro expanded hematopoietic stem cells

Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200‐fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non‐HSCs and single cell‐initiated cultures have substantial clone‐to‐clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non‐HSCs in expansion cultures. By directly linking single‐clone functional transplantation data with single‐clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This “repopulation signature” (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.     

Use of genetic markers to quantify bumblebee foraging range and nest density

Bumblebees (Hymenoptera: Apidae) are important pollinators of crops and wildflowers, but many species have suffered dramatic declines in recent decades. Strategies for their conservation require knowledge of their foraging range and nesting density, both of which are poorly understood. Previous studies have mainly focussed on the cosmopolitan bumblebee species Bombus terrestris , and implicitly assume this to be representative of other species. Here we use a landscape-scale microsatellite study to estimate the foraging range and nesting density of two ecologically dissimilar species, B. terrestris and B. pascuorum . Workers were sampled along a 10 km linear transect and 8–9 polymorphic microsatellite markers used to identify putative sisters. We provide the first published estimates of the number of colonies using a circle of radius 50 m in an agricultural landscape: 20.4 for B. terrestris and 54.7 for B. pascuorum . Estimates of nest density differed significantly between the two species: 13 km⁻² for B. terrestris and 193 km⁻² for B. pascuorum . Foraging ranges also differed substantially, with B. pascuorum foraging over distances less than 312 m and B. terrestris less than 625 m. Clearly bumblebee species differ greatly in fundamental aspects of their ecology. This has significant implications for the development of conservation strategies for rare bumblebees and isolated plant populations, for the management of bumblebees as pollinators, and for predicting patterns of gene flow from genetically modified plants.     

Flexible tethering of primase and DNA Pol α in the eukaryotic primosome

The Pol α/primase complex or primosome is the primase/polymerase complex that initiates nucleic acid synthesis during eukaryotic replication. Within the primosome, the primase synthesizes short RNA primers that undergo limited extension by Pol α. The resulting RNA–DNA primers are utilized by Pol δ and Pol ε for processive elongation on the lagging and leading strands, respectively. Despite its importance, the mechanism of RNA–DNA primer synthesis remains poorly understood. Here, we describe a structural model of the yeast primosome based on electron microscopy and functional studies. The 3D architecture of the primosome reveals an asymmetric, dumbbell-shaped particle. The catalytic centers of primase and Pol α reside in separate lobes of high relative mobility. The flexible tethering of the primosome lobes increases the efficiency of primer transfer between primase and Pol α. The physical organization of the primosome suggests that a concerted mechanism of primer hand-off between primase and Pol α would involve coordinated movements of the primosome lobes. The first three-dimensional map of the eukaryotic primosome at 25 Å resolution provides an essential structural template for understanding initiation of eukaryotic replication.     

Synthesis and structural characterisation of a novel polynuclear copper ribbon-like network. A study of its magnetic properties between 4 and 300 K

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Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to symptomatic infection. Adaptive immunity by Th1-type CD4(+) T cells and downstream cytokine responses are considered the predominant host defense mechanisms against mucosal Candida infections. However, numerous clinical and animal studies have indicated no or limited protective role of cells and cytokines of the Th1 or Th2 lineage against vaginal infection. The role for Th17 is only now begun to be investigated in-depth for VVC with results already showing significant controversy. On the other hand, a clinical live-challenge study and an established animal model have shown that a symptomatic condition is intimately associated with the vaginal infiltration of polymorphonuclear leukocytes (PMNs) but with no effect on vaginal fungal burden. Subsequent studies identified S100A8 and S100A9 alarmins as key chemotactic mediators of the acute PMN response. These chemotactic danger signals appear to be secreted by vaginal epithelial cells upon interaction and early adherence of Candida. Thus, instead of a putative immunodeficiency against Candida involving classical immune cells and cytokines of the adaptive response, the pathological inflammation in VVC is now considered a consequence of a non-productive innate response initiated by non-classical immune mediators.     

Lung fibroblast clones from normal and fibrotic subjects differ in hyaluronan and decorin production and rate of proliferation

Development of fibrosis involves an increase in the deposition of connective tissue components including collagens, fibronectin and proteoglycans. One hypothesis to account for matrix deposition in fibrosis is that fibroblast with differing matrix producing capacity are involved in the fibrotic process. To test this hypothesis, primary fibroblast cultures and clones derived from these primary lines were established from the lung tissue of control patients and patients with pulmonary fibrosis. The primary lines and derived clones were studied in relation to their capacity to proliferate and to produce proteoglycans and hyaluronan. Primary fibroblast cultures and clones from normal subjects and patients with lung fibrosis differed considerably, with up to 13-fold difference, in both hyaluronan and proteoglycan production. The major proteoglycan produced was decorin in both controls and cultures from fibrotic patients, while cultures from patients with lung fibrosis had a higher expression of mRNA for both collagen and decorin. Clones derived from a primary line from a fibrotic patient secreted 3-fold greater amounts of decorin than those from a control subject. Furthermore, a negative correlation between proliferation and synthesis of decorin was noted. We suggest that different fibroblast clones accumulate in the lung, and that specific cell populations of high decorin producing fibroblasts may exist which are crucial in the pathogenesis of fibrosis.