Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

ObjectiveTo examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life.DesignCohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure.SettingMaternity services in the Grampian region of Scotland.ParticipantsWomen selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970.ResultsThere were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4).ConclusionsHypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases.

What is already known on this topic

Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to womenRetrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life

What this study adds

Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertensionWomen who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart diseaseLong term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)     

Dipeptidyl nitrile inhibitors of Cathepsin L

A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.     

A new long-necked ‘sauropod-mimic’ stegosaur and the evolution of the plated dinosaurs

Stegosaurian dinosaurs have a quadrupedal stance, short forelimbs, short necks, and are generally considered to be low browsers. A new stegosaur, Miragaia longicollum gen. et sp. nov., from the Late Jurassic of Portugal, has a neck comprising at least 17 cervical vertebrae. This is eight additional cervical vertebrae when compared with the ancestral condition seen in basal ornithischians such as Scutellosaurus. Miragaia has a higher cervical count than most of the iconically long-necked sauropod dinosaurs. Long neck length has been achieved by ‘cervicalization’ of anterior dorsal vertebrae and probable lengthening of centra. All these anatomical features are evolutionarily convergent with those exhibited in the necks of sauropod dinosaurs. Miragaia longicollum is based upon a partial articulated skeleton, and includes the only known cranial remains from any European stegosaur. A well-resolved phylogeny supports a new clade that unites Miragaia and Dacentrurus as the sister group to Stegosaurus; this new topology challenges the common view of Dacentrurus as a basal stegosaur.     

Leptin increases maternal investment

The primary goal of virtually all organisms is to produce genetic offspring, thereby passing on their genes to future generations. Offspring production, however, is limited by available resources within an environment. Moreover, distributing sufficient energy among competing physiological systems is challenging and can result in trade-offs between self-maintenance and offspring investment when resources are limited. In the current study, we tested the hypothesis that the adipose hormone leptin is involved in mediating energetic trade-offs between competing physiological systems. Specifically, we tested the effects of elevated maternal leptin on investment into offspring production versus self maintenance (immune function), in the Siberian hamster (Phodopus sungorus). The current study provides the first evidence that leptin serves as a signal to mothers of available energy resulting in epigenetic effects. Therefore, elevated leptin allows females to retain more embryos to parturition, and rear more offspring to weaning via reduced maternal infanticide. Innate immune response was suppressed seemingly as a result of these enlarged litters, suggesting that the observed fitness increase is not without costs to the mother. Collectively, these findings suggest that leptin plays a critical role in allowing mothers to determine how much energy to invest in the production and care of young versus self-maintenance.     

The Structure of the Bacterial Oxidoreductase Enzyme DsbA in Complex with a Peptide Reveals a Basis for Substrate Specificity in the Catalytic Cycle of DsbA Enzymes

Oxidative protein folding in Gram-negative bacteria results in the formation of disulfide bonds between pairs of cysteine residues. This is a multistep process in which the dithiol-disulfide oxidoreductase enzyme, DsbA, plays a central role. The structure of DsbA comprises an all helical domain of unknown function and a thioredoxin domain, where active site cysteines shuttle between an oxidized, substrate-bound, reduced form and a DsbB-bound form, where DsbB is a membrane protein that reoxidizes DsbA. Most DsbA enzymes interact with a wide variety of reduced substrates and show little specificity. However, a number of DsbA enzymes have now been identified that have narrow substrate repertoires and appear to interact specifically with a smaller number of substrates. The transient nature of the DsbA-substrate complex has hampered our understanding of the factors that govern the interaction of DsbA enzymes with their substrates. Here we report the crystal structure of a complex between Escherichia coli DsbA and a peptide with a sequence derived from a substrate. The binding site identified in the DsbA-peptide complex was distinct from that observed for DsbB in the DsbA-DsbB complex. The structure revealed details of the DsbA-peptide interaction and suggested a mechanism by which DsbA can simultaneously show broad specificity for substrates yet exhibit specificity for DsbB. This mode of binding was supported by solution nuclear magnetic resonance data as well as functional data, which demonstrated that the substrate specificity of DsbA could be modified via changes at the binding interface identified in the structure of the complex.     

Ecological immunology: The organism in context

A major challenge in integrative biology is understanding the mechanisms by which organisms regulate trade-offs among various functions competing for limiting resources. Key among these competing processes is the maintenance of health and the production of offspring. Optimizing both, given limited resources, can prove challenging. The physiological and behavioral changes that occur during reproduction have been shown to greatly influence an organism's immune system, which can have consequences for susceptibility to disease. Likewise, investing in costly immunological defenses can impair reproductive function. However, the precise nature of these physiological and behavioral interactions appears to be greatly dependent upon the environmental context in which they occur. Here we take a comparative look at interactions between the reproductive and immune systems, including current immunological approaches, and discuss how similar studies can reveal vastly disparate results. Specifically, we highlight results from the ornate tree lizard (Urosuarus ornatus) and the Siberian hamster (Phodopus sungorus) model systems, which provide an example of current research in the field. Collectively, these results emphasize the importance of resource availability and an individual's energy stores for the existence of life-history trade-offs and the efficiency of physiological processes in general. Akin to Dobzhansky's famous line, like other aspects of biology, nothing in ecoimmunology seems to make sense except in the context of an organism's environment.     

Metakaryotic stem cell lineages in organogenesis of humans and other metazoans

A non-eukaryotic, metakaryotic cell with large, open mouthed, bell shaped nuclei represents an important stem cell lineage in fetal/juvenile organogenesis in humans and rodents. each human bell shaped nucleus contains the diploid human DNA genome as tested by quantitative Feulgen DNA cytometry and fluorescent in situ hybridization with human pan-telomeric, pan-centromeric and chromosome specific probes. From weeks ∼5–12 of human gestation the bell shaped nuclei are found in organ anlagen enclosed in sarcomeric tubular syncytia. Within syncytia bell shaped nuclear number increases binomially up to 16 or 32 nuclei; clusters of syncytia are regularly dispersed in organ anlagen. Syncytial bell shaped nuclei demonstrate two forms of symmetrical amitoses, facing or “kissing” bells and “stacking” bells resembling separation of two paper cups. Remarkably, DNA increase and nuclear fission occur coordinately. Importantly, syncytial bell shaped nuclei undergo asymmetrical amitoses creating organ specific ensembles of up to eight distinct closed nuclear forms, a characteristic required of a stem cell lineage. Closed nuclei emerging from bell shaped nuclei are eukaryotic as demonstrated by their subsequent increases by extra-syncytial mitoses populating the parenchyma of growing anlagen. From 9–14 weeks syncytia fragment forming single cells with bell shaped nuclei that continue to display both symmetrical and asymmetrical amitoses. These forms persist in the juvenile period and are specifically observed in bases of colonic crypts. Metakaryotic forms are found in organogenesis of humans, rats, mice and the plant Arabidopsis indicating an evolutionary origin prior to the divergence of plants and animals.     

Chancelloriid sclerites from the Lower Cambrian (Meishucunian) of eastern Yunnan,China, and the early history of the group

Chancelloriids are a group of enigmatic sessile animals that are covered with sclerites shaped as rosettes of spines, producing an appearance like that of a barrel cactus. They are known only from Cambrian rocks. Isolated sclerites of chancelloriids are widespread in small shelly faunas, but they have proven difficult to treat taxonomically due to the variation within and between individual animals. We report on large samples of chancelloriid sclerites from the Meishucunian (pre‐trilobitic Lower Cambrian) of eastern Yunnan Province, China, including material from the Dahai Member of the Zhujiaqing Formation (the Zhujiaqing section, Dahai, Huize County) and the Shiyantou Formation (the Xiaotan section, Yongshan County). The material from the Dahai Member appears to come from a single species, Chancelloriella irregularis. Statistical analysis of morphotype co‐occurrences in different samples suggests that several species are represented in the material from the Shiyantou Formation, which we herein tentatively place in four species, Allonnia erromenosa, Allonnia tetrathallis, Archiasterella charma sp. nov. and Archiasterella cf. pentactina. We suggest therefore that careful study of large collections of isolated chancelloriid sclerites permits the identification of different species, opening the possibility of their use in evolutionary or stratigraphical studies. In particular, in South China, it seems that Chancelloriella irregularis is characteristic of rocks of the Paragloborilus subglobosus – Purella squamulosa Assemblage Zone and the Watsonella crosbyi Assemblage Zone, whilst Archiasterella and Allonnia first appear in the overlying Sinosachites flabelliformis – Tannuolina zhangwentangi Assemblage Zone. C. irregularis is thus amongst the oldest well‐characterized chancelloriids, and the irregularity and poor organization of its sclerites relative to those of younger forms support the hypothesis that chancelloriid sclerites are compound structures arising from the fusion of originally separate elements, perhaps homologous with sclerites of halkieriids and other coeloscleritophorans. The similarity between the arrangement of rays in a chancelloriid sclerite and the arrangement of bubbles in small bubble clusters suggests that in many cases, aspects of the form of chancelloriid sclerites are the result of simple physical processes.     

Taxonomic identification bias does not drive patterns of abundance and diversity in theropod dinosaurs

The ability of palaeontologists to correctly diagnose and classify new fossil species from incomplete morphological data is fundamental to our understanding of evolution. Different parts of the vertebrate skeleton have different likelihoods of fossil preservation and varying amounts of taxonomic information, which could bias our interpretations of fossil material. Substantial previous research has focused on the diversity and macroevolution of non-avian theropod dinosaurs. Theropods provide a rich dataset for analysis of the interactions between taxonomic diagnosability and fossil preservation. We use specimen data and formal taxonomic diagnoses to create a new metric, the Likelihood of Diagnosis, which quantifies the diagnostic likelihood of fossil species in relation to bone preservation potential. We use this to assess whether a taxonomic identification bias impacts the non-avian theropod fossil record. We find that the patterns of differential species abundance and clade diversity are not a consequence of their relative diagnosability. Although there are other factors that bias the theropod fossil record that are not investigated here, our results suggest that patterns of relative abundance and diversity for theropods might be more representative of Mesozoic ecology than often considered.