Localization to the nucleolus is a common feature of coronavirus nucleoproteins and the protein may disrupt host cell division

The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G2/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.

The role of temperament and family environment in the development of anxiety disorder: two-year follow-up

Objective Behavioural inhibition (BI) in early childhood is associated with increased risk for anxiety. The present research examines BI alongside family environment factors, specifically maternal negativity and overinvolvement, maternal anxiety and mother-child attachment, with a view to providing a broader understanding of the development of child anxiety. Method Participants were 202 children classified at age 4 as either behaviourally inhibited (N=102) or uninhibited (N=100). Family environment, BI and child anxiety were assessed at baseline and child anxiety and BI were assessed again two-years later when participants were aged 6 years. Results After controlling for baseline anxiety, inhibited participants were significantly more likely to meet criteria for a diagnosis of social phobia and generalized anxiety disorder at follow-up. Path analysis suggested that maternal anxiety significantly affected child anxiety over time, even after controlling for the effects of BI and baseline anxiety. No significant paths from parenting or attachment to child anxiety were found. Maternal overinvolvement was significantly associated with BI at follow-up. Conclusions At age 4, BI, maternal anxiety and child anxiety represent risk factors for anxiety at age 6. Furthermore, overinvolved parenting increases risk for BI at age 6, which may then lead to the development of anxiety in later childhood.

Temperament, family environment and anxiety in preschool children

This research examines the relationship between behavioural inhibition (BI), family environment (overinvolved and negative parenting, parental anxiety and parent-child attachment) and anxiety in a sample of 202 preschool children. Participants were aged between 3 years 2 months and 4 years 5 months, 101 were male. A thorough methodology was used that incorporated data from multiple observations of behaviour, diagnostic interviews and questionnaire measures. The results showed that children categorised as behaviourally inhibited were significantly more likely to meet criteria for a range of anxiety diagnoses. Furthermore, a wide range of family environment factors, including maternal anxiety, parenting and attachment were significantly associated with BI, with inhibited children more likely to experience adverse family environment factors. No interactions between temperament and family environment were found for child anxiety. However, a significant relationship between current maternal anxiety and child anxiety was found consistently even after controlling for BI. Additionally, there was some evidence of a relationship between maternal negativity and child anxiety, after controlling for BI. The results may suggest that temperament and family environment operate as additive, rather than interactive risk factors for child anxiety. This is discussed in the context of theoretical models of child anxiety and directions for future research.

Another look at family adjustment

This chapter argues that in the international career context there is a need to conceptualise the adjustment of the family unit holistically. We discuss what that means and how it can be done. We note that to date the family has almost always been conceptualised as a hindrance to or a support for the working expatriate. However, in international assignments the family as a whole is expatriated and the family may become part of the expatriate resources with the line between work and family/personal life blurring. We draw on the Family Adjustment and Adaptation Response (FAAR) literature to argue that previous conceptions of adjustment have failed to capture the complexity of the process from the family perspective and we use that literature to develop our understanding of the process of adjustment of the family unit and suggest ways forward.

Diallyl disulfide-induced apoptosis in a breast-cancer cell line (MCF-7) may be caused by inhibition of histone de-acetylation

The health benefits of garlic have been proven by epidemiological and experimental studies. Diallyl disulphide (DADS), the major organosulfur compound found in garlic oil, is known to lower the incidence of breast cancer both in vitro and in vivo. The studies reported here demonstrate that DADS induces apoptosis in the MCF-7 breast-cancer cell line through interfering with cell-cycle growth phases in a way that increases the sub-G0 population and substantially halts DNA synthesis. DADS also induces phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane and activates caspase-3. Further studies revealed that DADS modulates the cellular levels of Bax, Bcl-2, Bcl-xL and Bcl-w in a dose-dependent manner, suggesting the involvement of Bcl-2 family proteins in DADS induced apoptosis. Histone deacetylation inhibitors (HDACi) are known to suppress cancer growth and induce apoptosis in cancer cells. Here it is shown that DADS has HDACi properties in MCF-7 cells as it lowers the removal of an acetyl group from an acetylated substrate and induces histone-4 (H4) hyper-acetylation. The data thus indicate that the HDACi properties of DADS may be responsible for the induction of apoptosis in breast cancer cells.

The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P ≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P ≤0.05). In addition, lactoferrin (P ≤0.002), transferrin receptor (P ≤0.05) and solute carrier family 11A1 (P ≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.

The application of a domains based analysis to family processes: implications for assessment and therapy

Social domains are classes of interpersonal processes each with distinct procedural rules underpinning mutual understanding, emotion regulation and action. We describe the features of three domains of family life – safety, attachment and discipline/expectation – and contrast them with exploratory processes in terms of the emotions expressed, the role of certainty versus uncertainty, and the degree of hierarchy in an interaction. We argue that everything that people say and do in family life carries information about the type of interaction they are engaged in – that is, the domain. However, sometimes what they say or how they behave does not make the domain clear, or participants in the social interactions are not in the same domain (there is a domain mismatch). This may result in misunderstandings, irresolvable arguments or distress. We describe how it is possible to identify domains and judge whether they are clear and unclear, and matched and mismatched, in observed family interactions and in accounts of family processes. This then provides a focus for treatment and helps to define criteria for evaluating outcomes.

Struggles over family land? Tree crops, land and labour in Ghana's Brong-Ahafo region

Agricultural land use in much of Brong-Ahafo region, Ghana has been shifting from the production of food crops towards increased cashew nut cultivation in recent years. This article explores everyday, less visible, gendered and generational struggles over family farms in West Africa, based on qualitative, participatory research in a rural community that is becoming increasingly integrated into the global capitalist system. As a tree crop, cashew was regarded as an individual man's property to be passed on to his wife and children rather than to extended family members, which differed from the communal land tenure arrangements governing food crop cultivation. The tendency for land, cash crops and income to be controlled by men, despite women's and young people's significant labour contributions to family farms, and for women to rely on food crop production for their main source of income and for household food security, means that women and girls are more likely to lose out when cashew plantations are expanded to the detriment of land for food crops. Intergenerational tensions emerged when young people felt that their parents and elders were neglecting their views and concerns. The research provides important insights into gendered and generational power relations regarding land access, property rights and intra-household decision-making processes. Greater dialogue between genders and generations may help to tackle unequal power relations and lead to shared decision-making processes that build the resilience of rural communities.

Vivipary in the cactus family: A reply to Ortega-Baes` et al. evaluation of 25 species from northwestern Argentina

This is a reply to Ortega-Baes` et al. (2010) survey of 25 Argentinean species of cacti evaluated for vivipary. We argue that the sample size and geographic area of the species investigated is insufficient to totally exclude the putative commonness of this condition in the Cactaceae. We indicate possible reasons why they did not find viviparous fruits in their survey. Failure to detect vivipary in cacti of NW Argentina may be correlated with limited taxonomic sampling and geographic region in addition to intrinsic and extrinsic plant factors, including different stages of fruit and seed development and genetic, ecological, and edaphic aspects, which, individually or in concert, control precocious germination. We uphold that viviparity is putatively frequent in this family and list 16 new cases for a total of 53 viviparous cacti, which make up ca. 4% incidence of viviparism in the Cactaceae, a substantially higher percentage than most angiosperm families exhibiting this condition. The Cactaceae ranks fourth in frequency of viviparity after the aquatic families of mangroves and seagrasses. We suggest the re-evaluation of cactus vivipary, primarily as a reproductive adaptation to changing environments and physiological stress with a secondary role as a reproductive strategy with limited offspring dispersal/survival and fitness advantages. (C) 2011 Elsevier Ltd. All rights reserved.

Transcriptional memory and switching in the Plasmodium falciparum rif gene family

The human malaria parasite Plasmodium falciparum expresses erythrocyte-surface directed variant antigens which are important virulence factors Many are transcribed from multigene families and presumably their mode of expression is strictly controlled to guarantee immune evasion in the human host. In order to elucidate the dynamics of rif transcription and to investigate if rif switching is comparable to var switching we monitored rif variant gene expression in parasites with different cytoadhesive properties as well as after a number of reinvasions. We found identical transcripts in parasite lines with different adhesive phenotypes suggesting that rif genes do not have a critical role in determining the cytoadhesion specificity of infected erythrocytes. We show for the first time that rif genes may show a conserved mode of transcription, maintaining the previously dominant rif transcript in subsequent reinvasions, but also observed rapid switching at rates up to 45% per generation, much higher than for the var gene family. (C) 2009 Elsevier B.V. All rights reserved.

Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar)

BACKGROUND: Canalization is defined as the stability of a genotype against minor variations in both environment and genetics. Genetic variation in degree of canalization causes heterogeneity of within-family variance. The aims of this study are twofold: (1) quantify genetic heterogeneity of (within-family) residual variance in Atlantic salmon and (2) test whether the observed heterogeneity of (within-family) residual variance can be explained by simple scaling effects. RESULTS: Analysis of body weight in Atlantic salmon using a double hierarchical generalized linear model (DHGLM) revealed substantial heterogeneity of within-family variance. The 95% prediction interval for within-family variance ranged from ~0.4 to 1.2 kg2, implying that the within-family variance of the most extreme high families is expected to be approximately three times larger than the extreme low families. For cross-sectional data, DHGLM with an animal mean sub-model resulted in severe bias, while a corresponding sire-dam model was appropriate. Heterogeneity of variance was not sensitive to Box-Cox transformations of phenotypes, which implies that heterogeneity of variance exists beyond what would be expected from simple scaling effects. CONCLUSIONS: Substantial heterogeneity of within-family variance was found for body weight in Atlantic salmon. A tendency towards higher variance with higher means (scaling effects) was observed, but heterogeneity of within-family variance existed beyond what could be explained by simple scaling effects. For cross-sectional data, using the animal mean sub-model in the DHGLM resulted in biased estimates of variance components, which differed substantially both from a standard linear mean animal model and a sire-dam DHGLM model. Although genetic differences in canalization were observed, selection for increased canalization is difficult, because there is limited individual information for the variance sub-model, especially when based on cross-sectional data. Furthermore, potential macro-environmental changes (diet, climatic region, etc.) may make genetic heterogeneity of variance a less stable trait over time and space.

Cedric Gael Bryant, Lee Family Professor of English

Cedric Gael Bryant, Lee Family Professor of English, reading Beloved: A Novel, by Toni Morrison (PS3563 O8749 B4 1987)

Jorge Olivares, Allen Family Professor of Latin American Literature

Jorge Olivares, Allen Family Professor of Latin American Literature reading Sexual injustice : Supreme Court decisions from Griswold to Roe by Marc Stein

New evidence of the causal effect of family size on child quality in a developing country

This paper presents new evidence of the causal effect of family size on child quality in a developing-country context. We estimate the impact of family size on child labor and educational outcomes among Brazilian children and young adults by exploring the exogenous variation of family size driven by the presence of twins in the family. Using the Brazilian Census data for 1991, we nd that the exogenous increase in family size is positively related to labor force participation for boys and girls and to household chores for young women. We also and negative e ects on educational outcomes for boys and girls and negative impacts on human capital formation for young female adults. Moreover, we obtain suggestive evidence that credit and time constraints faced by poor families may explain the findings.

Dynamical erosion of asteroid groups in the region of the Phocaea family

In a previous paper, the current state of knowledge of the region containing the Phocaea dynamical family was revised. Here, the dynamical evolution and possible origin of the Phocaea dynamical family and asteroid groups in the region are investigated. First, I study the case of asteroids at high eccentricity (e > 0.31). I find that these objects are unstable because of encounters with Mars on time-scales of up to 270 Myr. The minimum time needed by members of the Phocaea classical family to reach the orbital locations of these objects, 370 Myr, can be used to set a lower limit on the age of the Phocaea family.Next, attention is focused on the chaotic layer previously identified near the nu(6) secular resonance border. Using analytical and numerical tools, I find that the presence of the nu(6) secular resonance forces asteroids with vertical bar g-g(6)vertical bar < 2.55 arcsec yr(-1) to reach eccentricities high enough to allow them to experience deep, close encounters with Mars. Results of the analytical model of Yoshikawa and of my numerical simulations fully explain the low-inclination chaotic region found by Carruba.Finally, I investigate the long-term stability of the minor families and clumps identified in the previous paper, with particular emphasis on a clump only identifiable in the domain of proper frequencies (n, g, g - s) around (6246) Komurotoru. I find that while the clumps identified in the space of proper elements quickly disperse when the Yarkovsky effect is considered, the family around (19536) is still observable for time-scales of more than 50 Myr. The (6246) clump, characterized by its interaction with the nu(5) + nu(16) and 2 nu(6) - nu(16) secular resonances, is robust on time-scales of 50 Myr. I confirm that this group may be the first clump ever detected in the frequency domain that can be associated with a real collisional event.