The outer core lipopolysaccharide of Salmonella enterica serovar Typhi is required for bacterial entry into epithelial cells

Salmonella enterica serovar Typhi causes typhoid fever in humans. Central to the pathogenicity of serovar Typhi is its capacity to invade intestinal epithelial cells. The role of lipopolysaccharide (LPS) in the invasion process of serovar Typhi is unclear. In this work, we constructed a series of mutants with defined deletions in genes for the synthesis and polymerization of the O antigen (wbaP, wzy, and wzz) and the assembly of the outer core (waaK, waaJ, waaI, waaB, and waaG). The abilities of each mutant to associate with and enter HEp-2 cells and the importance of the O antigen in serum resistance of serovar Typhi were investigated. We demonstrate here that the presence and proper chain length distribution of the O-antigen polysaccharide are essential for serum resistance but not for invasion of epithelial cells. In contrast, the outer core oligosaccharide structure is required for serovar Typhi internalization in HEp-2 cells. We also show that the outer core terminal glucose residue (Glc II) is necessary for efficient entry of serovar Typhi into epithelial cells. The Glc I residue, when it becomes terminal due to a polar insertion in the waaB gene affecting the assembly of the remaining outer core residues, can partially substitute for Glc II to mediate bacterial entry into epithelial cells. Therefore, we conclude that a terminal glucose in the LPS core is a critical residue for bacterial recognition and internalization by epithelial cells.

Intra-uterine growth restriction and increased risk of hypertension in adult life: A follow-up study of 50-year-olds

OBJECTIVE:

To compare blood pressure between 50-year-old adults who were born at term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR; birth weight <10th centile) and a control group of similar age born at term without IUGR (birth weight =10th centile).

STUDY DESIGN:

Controlled comparative study.

METHODS:

Participants included 232 men and women who were born at the Royal Maternity Hospital, Belfast, a large regional maternity hospital in Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were born with IUGR were compared with 124 controls with normal birth weight for gestation. The main outcome measures were systolic and diastolic blood pressure at approximately 50 years of age, measured according to European recommendations.

RESULTS:

The IUGR group had higher systolic and diastolic blood pressure than the control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI 124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg, respectively. After adjustment for gender, the differences between the groups were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More participants in the IUGR group were receiving treatment for high blood pressure compared with the control group [16 (15%) vs 11 (9%)], although this was not statistically significant. The proportion of subjects with blood pressure >140/90 mmHg or currently receiving antihypertensive treatment was 45% (n = 49) for the IUGR group, and 31% (n = 38) for the control group (odds ratio 1.9, 95% CI 1.1-3.3). Adjustment for potential confounders made little difference.

CONCLUSIONS:

IUGR is associated with higher blood pressure at 50 years of age. Individuals born with IUGR should have regular blood pressure screening and early treatment as required. Hypertension remains underdiagnosed and undertreated in adult life.

Risk-Taking Differences Across the Adult Life Span:A Question of Age and Domain

Older adults face important risky decisions about their health, their financial future, and their social environment. We examine age differences in risk-taking behaviors in multiple risk domains across the adult life span.

Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of NPY signalling and hypertension in adult life

Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1–5 and 6–10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mmHg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease

Families with multiple problems: Some challenges in identifying and providing services to those experiencing adversities across the life course

Summary A concern amongst policy makers to identify high cost and low productivity populations has created a new interest in identifying those who experience adversities across the life-course. This paper outlines the development of conceptual understandings of families whose children experience multiple adversities and links this with later poor outcomes in adult life and examines some of the research challenges in establishing such linkages. Findings It is argued that current thinking with regard to these issues reflects historical domains within which services to children and to adults are located. The challenge to domain thinking is both horizontal and vertical. Policy being required to address the horizontal axis by co-ordinating planned approaches to multiple needs across services. And policy being necessary to address the vertical cleavage between children’s and adult services in ways which join up services across the life path; conceptually and practically acknowledging the links between child and adult experiences. Application Such policy developments will inevitably require social work to develop alternative paradigms for understanding the needs of children and adults and designing services to effectively meet these.

Concise Review: Stem Cell Effects in Radiation Risk

Stem cells of normal mammalian tissues are defined as nonspecialized cells that have two critical properties: (a) the ability to renew themselves through cell division and (b) the potency to differentiate into other cell types. Therefore, they play a crucial role in development and in tissue homeostasis during adult life. Being long-lived, they can be the targets of environmental carcinogens leading to the accumulation of consecutive genetic changes. Hence, the genome of stem cells must be exceptionally well protected, and several protective mechanisms have evolved to ensure the genetic integrity of the stem cell compartment in any given tissue. Ionizing radiation exposure can disrupt tissue homeostasis both through the induction of cell killing/depletion of radiosensitive stem cells, leading to loss of tissue functionality and by genotoxic damage, increasing overall risk of cancer. We will review the current knowledge about radiation effects in adult stem cells of specific normal tissues, including skin, breast, and brain, examine parallels, as well as differences with cancer stem cells, and discuss the relevance of stem cell effects to radiation risk and radiotherapy. STEM CELLS 2011;29:1315-1321

Irish study on high-density schizophrenia families:field methods and power to detect linkage

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one whom had schizophrenia (S) or poor-outcome schizo-affective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. The phenotypic sample contained 277 pedigrees and 1,770 individuals and the linkage sample 265 pedigrees and 1,408 individuals. Using the intermediate definition of affection, the phenotypic sample contained 837 affected individuals and 526 affected sibling pairs. Parallel figures for the linkage sample were 700 and 420. Individuals with schizophrenia from these multiplex pedigrees resembled epidemiologically sampled cases with respect to age at onset, gender distribution, and most clinical symptoms, although they were more thought-disordered and had a poorer outcome. Power analyses based on the model of linkage heterogeneity indicated that the ISHDSF should be able to detect a major locus that influences susceptibility to schizophrenia in as few as 20% of families. Compared to first-degree relatives of epidemiologically sampled schizophrenic probands, first-degree relatives of schizophrenic members from the ISHDSF had a similar risk for schizotypal personality disorder, affective illness, alcoholism, and anxiety disorder. With sufficient resources, large-scale ascertainment of multiplex schizophrenia pedigrees is feasible, especially in countries with catchmented psychiatric care and stable populations. Although somewhat more severely ill, schizophrenic members of such pedigrees appear to clinically resemble typical schizophrenic patients. Our ascertainment process for multiplex schizophrenia families did not select for excess familial risk for affective illness or alcoholism. With its large sample ascertained in a standardized manner from a relatively homogeneous population, the ISHDSF provides considerable power to detect susceptibility loci for schizophrenia.

Family Economic Vulnerability & the Great Recession: An Analysis of the First two Waves of the Growing Up in Ireland Study

In this paper we make use of the first and second waves of the 2008 and 1998 cohorts of the Growing Up in Ireland study, to develop a multidimensional and dynamic approach to understanding the impact on families and children in Ireland of the Great Recession. Economic vulnerability is operationalised as involving a distinctive risk profile in relation to relative income, household joblessness and economic stress. We find that the recession was associated with a significant increase in levels of economic vulnerability and changing risk profiles involving a more prominent role for economic stress for both the 2008 and 1998 cohorts. The factors affecting vulnerability outcomes were broadly similar for both cohorts. Persistent economic vulnerability was significantly associated with lone parenthood, particularly for those with more than one child, lower levels of Primary Care Giver (PCG) education and to a lesser extent younger age of PCG at child’s birth, number of children and a parent leaving or dying. Similar factors were associated with transient vulnerability in the first wave but the magnitude of the effects was significantly weaker particularly in relation to lone parenthood and level of education of the PCG. For entry into vulnerability the impact of these factors was again substantially weaker than for persistent and transient vulnerability indicating a significantly greater degree of socio-economic heterogeneity among the group that became vulnerable during the recession. The findings raise policy and political problems that go beyond those associated with catering for groups that have tended to be characterized by high dependence on social welfare.

Satellite flies (Leucophora personata, Diptera : Anthomyiidae) and other dipteran parasites of the communal bee Andrena agilissima (Hymenoptera : Andrenidae) on the island of Elba, Italy

Solitary and presocial aculueate Hymenoptera are parasitized by a range of dipteran species in the families Axithomyiidae, Bombyliidae, Conopidae, Phoridae, and Sarcophagidae that are likely to impact on their hosts. We undertook a study over several years of a univoltine and communal bee, Andrena agilissima, and its main dipteran parasites, in particular the satellite fly Leucophora personata (Diptera: Anthomyiidae). Behavioural and ecological data were collected from one nesting aggregation of the host bee on the island of Elba, Italy, from 1993 to 2003, and from a foraging site of the bee, ca 5 km from the nesting aggregation. Other Diptera associated with A. agilissmia at the field site were the bee fly Bombylius fimbriatus (Bombyliidae), the conopid fly Zodion cinereum (Conopidae), and the scuttle fly Megaselia andrenae (Phoridae). The phenology of the Diptera broadly overlapped with that of their host across the season of activity (end of April and all of May). Diurnal activity patterns differed slightly; L. personata in particular was active at the host's nesting site before A. agilissima. Female satellite flies also showed a range of behaviours in gaining entry to a host nest. We summarize published data on this and other Leucophora species that parasitize Andrena host bees. Host bees returning to their nests occasionally undertook zig-zag flight manoeuvres if followed by a satellite fly that were generally successful in evading the fly. Satellite flies that entered a nest, presumably to oviposit, were less likely to remain therein if another host bee entered the same nest, suggesting that one advantage to communal nesting for this host is a reduction in brood cell parasitism by L. personata. We provide the first clear evidence for parasitism by a Zodion of any Andrena host. Both L. personata and M. andrenae concentrated their parasitic activities in the zone of the host nesting aggregation with highest nest densities. Three of the Diptera, L. personata, B. fimbriatus, and Z. cinereum, seemed to have extremely low rates of parasitism whilst that of M. andrenae appeared low. Though they have refined parasitic behaviour that allows them to gain entry into host nests (L. personata, B. fimbriatus, and M. andrenae) or to parasitize adults (Z. cinercum), these parasites seem not to impact upon the dynamics of the host A. agilissima at the nesting aggregation, and the host possesses traits to reduce parasitism.

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA: n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations. (C) 2008 Elsevier Ltd. All rights reserved.

Cardiovascular and metabolic abnormalities in the offspring of diabetic pregnancy

Aims/hypothesis. Maternal fuel metabolism is known to exert long range effects on the later development of children of diabetic mothers. Recently cardiovascular disease in adult life has been linked retrospectively with foetal malnutrition. The aim of this study was to identify whether markers for fuel-related cardiovascular programming exist for the offspring of diabetic pregnancy.