Marriage Timing over the Generations

Strong relationships have been hypothesized between the timing of marriage and the familial environment of the couple. Sociologists have identified various mechanisms via which the age at marriage in the parental generation might be related to the age at marriage of the children. In our paper we study this relationship for historical populations. We use a dataset consisting of several hundreds of thousands of marriages contracted in three of the 11 Dutch provinces between 1812 and 1922. We identified the generational links between the brides, grooms, their parents, and grandparents. We studied (a) whether there is a relationship between ages at marriage of (grandfathers) fathers and sons, and ages at marriage of (grandmothers) mothers and daughters and (b) whether this relationship might be explained by social class. We find evidence for a clear effect of the family on age at marriage and substantial intergenerational transmission. The impact that the family of origin has on age at entry into marriage can partly be attributed to social class. We also observed positive effects of grandparents’ age at marriage on their offspring’s age at marriage.

Species distribution and <Emphasis Type="Italic">in vitro</Emphasis> antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

Background  

In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis.     

Photoinduced electron-transfer in perylenediimide triphenylamine-based dendrimers: single photon timing and femtosecond transient absorption spectroscopy.

The excited state dynamics of two generations perylenediimide chromophores substituted in the bay area with dendritic branches bearing triphenylamine units as well as those of the respective reference compounds are investigated. Using single photon timing and multi-pulse femtosecond transient absorption experiments a direct proof of a reversible charge transfer occurring from the peripheral triphenylamine to the electron acceptor perylenediimide core is revealed. Femtosecond pump-dump-probe experiments provide evidence for the ground state dynamics by populating excited vibronic levels. It is found by the means of both techniques that the rotational isomerization of the dendritic branches occurs on a time scale that ranges up to 1 ns. This time scale of the isomerization depends on the size of the dendritic arms and is similar both in the ground and excited state.     

The cell wall of the human pathogen Candida glabrata: differential incorporation of novel adhesin-like wall proteins

The cell wall of the human pathogen Candida glabrata governs initial host-pathogen interactions that underlie the establishment of fungal infections. With the aim of identifying species-specific features that may directly relate to its virulence, we have investigated the cell wall of C. glabrata using a multidisciplinary approach that combines microscopy imaging, biochemical studies, bioinformatics, and tandem mass spectrometry. Electron microscopy revealed a bilayered wall structure in which the outer layer is packed with mannoproteins. Biochemical studies showed that C. glabrata walls incorporate 50% more protein than Saccharomyces cerevisiae walls and, consistent with this, have a higher mannose/glucose ratio. Evidence is presented that C. glabrata walls contain glycosylphosphatidylinositol (GPI) proteins, covalently bound to the wall 1,6-β-glucan, as well as proteins linked through a mild-alkali-sensitive linkage to 1,3-β-glucan. A comprehensive genome-wide in silico inspection showed that in comparison to other fungi, C. glabrata contains an exceptionally large number, 67, of genes encoding adhesin-like GPI proteins. Phylogenetically these adhesin-like proteins form different clusters, one of which is the lectin-like EPA family. Mass spectrometric analysis identified 23 cell wall proteins, including 4 novel adhesin-like proteins, Awp1/2/3/4, and Epa6, which is involved in adherence to human epithelia and biofilm formation. Importantly, the presence of adhesin-like proteins in the wall depended on the growth stage and on the genetic background used, and this was reflected in alterations in adhesion capacity and cell surface hydrophobicity. We propose that the large repertoire of adhesin(-like) genes of C. glabrata contributes to its adaptability and virulence.     

Results of the Ontario Survey on the Prevalence and Control of Hypertension

Background

Available information on the prevalence and management of hypertension in the Canadian population dates back to 1986–1992 and probably does not reflect the current status of this major risk factor for cardiovascular disease. We sought to evaluate the current prevalence and management of hypertension among adults in the province of Ontario.

Methods

Potential respondents from randomly selected dwellings within target neighbourhoods in 16 municipalities were contacted at their homes to request participation in the study. For potential respondents who agreed to participate, blood pressure was measured with an automated device. Estimation weights were used to obtain representative estimates of population parameters. Responses were weighted to the total adult population in Ontario of 7 996 653.

Results

From 6436 eligible dwellings, contact was made with 4559 potential participants, of whom 2992 agreed to participate. Blood pressure measurements were obtained for 2551 of these respondents (age 20–79 years). Hypertension, defined as systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 90 mm Hg or more, or treatment with an antihypertensive medication, was identified in 21.3% of the population overall (23.8% of men and 19.0% of women). Prevalence increased with age, from 3.4% among participants 20–39 years of age to 51.6% among those 60–79 years of age. Hypertension was more common among black people and people of South Asian background than among white people; hypertension was also associated with higher body mass index. Among participants with hypertension, 65.7% were undergoing treatment with control of hypertension, 14.7% were undergoing treatment but the hypertension was not controlled, and 19.5% were not receiving any treatment (including 13.7% who were unaware of their hypertension). The extent of control of hypertension did not differ significantly by age, sex, ethnic background or comorbidities.

Interpretation

In Ontario, the overall prevalence of hypertension is high in the older population but appears not to have increased in recent decades. Hypertension management has improved markedly among all age groups and for both sexes.Hypertension is a major risk factor for premature cardiovascular morbidity and mortality. Epidemiologic studies have indicated that, for people 40–69 years of age, each increase of 20 mm Hg in usual systolic blood pressure is associated with a doubling of mortality rates for stroke and ischemic heart disease.¹ In 2002 the World Health Organization estimated that at least 50% of cases of cardiovascular disease and at least 75% of strokes were caused by elevated blood pressure.² At the same time, randomized clinical trials have demonstrated that these risks can be markedly reduced by antihypertensive drug therapy. The substantial burden of suffering associated with hypertension, combined with the availability of feasible and accurate means of detection and a clear benefit from treatment have led to worldwide recommendations for hypertension screening and management.Currently available Canadian data on the prevalence and management of hypertension are based on Canadian Heart Health Surveys that took place between 1986 and 1992. At that time, 22% of adult Canadians had hypertension, but only 16% of these had their blood pressure treated and controlled.³ These data are clearly out of date, and there has been no way of assessing the impact of changes in lifestyle, including higher rates of obesity and a sedentary lifestyle, on the prevalence of hypertension or determining whether hypertension management has improved with the widespread use of newer classes of antihypertensive drugs such as calcium antagonists and blockers of the renin–angiotensin system.We sought to evaluate the current prevalence and management of hypertension among adults in the province of Ontario.     

Detection and structural investigation of metabolites of stanozolol in human urine by liquid chromatography tandem mass spectrometry

The applicability of LC–MS/MS in precursor ion scan mode for the detection of urinary stanozolol metabolites has been studied. The product ion at m/z 81 has been selected as specific for stanozolol metabolites without a modification in A- or N-rings and the product ions at m/z 97 and 145 for the metabolites hydroxylated in the N-ring and 4-hydroxy-stanozolol metabolites, respectively. Under these conditions, the parent drug and up to 15 metabolites were found in a positive doping test sample. The study of a sample from a chimeric uPA-SCID mouse collected after the administration of stanozolol revealed the presence of 4 additional metabolites. The information obtained from the product ion spectra was used to develop a SRM method for the detection of 19 compounds. This SRM method was applied to several doping positive samples. All the metabolites were detected in both the uPA-SCID mouse sample and positive human samples and were not detected in none of the blank samples tested; confirming the metabolic nature of all the detected compounds. In addition, the application of the SRM method to a single human excretion study revealed that one of the metabolites (4ξ,16ξ-dihydroxy-stanozolol) could be detected in negative ionization mode for a longer period than those commonly used in the screening for stanozolol misuse (3′-hydroxy-stanozolol, 16β-hydroxy-stanozolol and 4β-hydroxy-stanozolol) in doping analysis. The application of the developed approach to several positive doping samples confirmed the usefulness of this metabolite for the screening of stanozolol misuse. Finally, a tentative structure for each detected metabolite has been proposed based on the product ion spectra measured with accurate masses using UPLC–QTOF MS.     

The Potential of Tree Rings for the Study of Forest Succession in Southern Mexico

Studies of tropical secondary forest succession face strong limitations due to the slow pace of succession and the time-consuming task of monitoring processes. The occurrence of tree rings in secondary forest trees may help expand our knowledge on succession in these systems and may be useful for fallow dating in chronosequence studies. We examine here the potential of tree rings to study forest succession by sampling 70 species along chronosequences of dry and wet forests in southern Mexico. Based on wood anatomical features, we estimated that about 37 percent of the species presented distinct growth rings useful for ring studies. Overall, maximum number of rings matched well the interview-based fallow ages but, at some sites, trees had consistently higher numbers of rings, probably due to errors in fallow ages derived from interviews. Best fallow age estimations were obtained by examining rings in both pioneer and nonpioneer species. Reconstruction of species' establishment dates revealed that pioneer and nonpioneer species establish early during succession, and that species of both groups continue to recruit after many years. Our study clearly shows that tree ring analysis is a promising tool for studies on secondary forest succession in the tropics.     

Adenylate cyclase regulates elongation of mammalian primary cilia

The primary cilium is a non-motile microtubule-based structure that shares many similarities with the structures of flagella and motile cilia. It is well known that the length of flagella is under stringent control, but it is not known whether this is true for primary cilia. In this study, we found that the length of primary cilia in fibroblast-like synoviocytes, either in log phase culture or in quiescent state, was confined within a range. However, when lithium was added to the culture to a final concentration of 100 mM, primary cilia of synoviocytes grew beyond this range, elongating to a length that was on average approximately 3 times the length of untreated cilia. Lithium is a drug approved for treating bipolar disorder. We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation. Inhibition of GSK-3β by four different inhibitors did not induce primary cilia elongation. ACIII was found in primary cilia of a variety of cell types, and lithium treatment of these cell types led to their cilium elongation. Further, we demonstrate that different cell types displayed distinct sensitivities to the lithium treatment. However, in all cases examined primary cilia elongated as a result of lithium treatment. In particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human astrocytes, developed long primary cilia when lithium was used at or close to the therapeutic relevant concentration (1–2 mM). These results suggest that the length of primary cilia is controlled, at least in part, by the ACIII–cAMP signaling pathway.     

Role of the inhibitory KIR ligand HLA-Bw4 and HLA-C expression levels in the recognition of leukemic cells by Natural Killer cells

Transplantation of acute myeloid leukemia (AML) patients with grafts from related haploidentical donors has been shown to result in a potent graft-versus-leukemia effect. This effect is mediated by NK cells because of the lack of activation of inhibitory killer cell immunoglobulin-like receptors (KIRs) which recognize HLA-Bw4 and HLA-C alleles. However, conflicting results have been reported about the impact of KIR ligand mismatching on the outcome of unrelated HLA-mismatched hematopoietic stem cells transplants (HSCT) to leukemic patients. The interpretation of these conflicting results is hampered by the scant information about the level of expression of HLA class I alleles on leukemic cells, although this variable may affect the activation of inhibitory KIRs. Therefore in the present study, utilizing a large panel of human monoclonal antibodies we have measured the level of expression of HLA-A, -B and -C alleles on 20 B-chronic lymphoid leukemic (B-CLL) cell preparations, on 16 B-acute lymphoid leukemic (B-ALL) cell preparations and on 19 AML cell preparations. Comparison of the level of HLA class I antigen expression on leukemic cells and autologous normal T cells identified selective downregulation of HLA-A and HLA-B alleles on 15 and 14 of the 20 B-CLL, on 2 and 5 of the 16 B-ALL and on 7 and 11 of the 19 AML patients tested, respectively. Most interestingly HLA-C alleles were markedly downregulated on all three types of leukemic cells; the downregulation was most pronounced on AML cells. The potential functional relevance of these abnormalities is suggested by the dose-dependent enhancement of NK cell activation caused by coating the HLA-HLA-Bw4 epitope with monoclonal antibodies on leukemic cells which express NK cell activating ligands. Our results suggest that besides the HLA and KIR genotype, expression levels of KIR ligands on leukemic cells should be included among the criteria used to select the donor-recipient combinations for HSCT.