Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study

Objective: To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses. Design: Population based cohort study. Subjects: 1 026 249 pregnancies without congenital malformations. Setting: Sweden 1983-92. Main outcome measure: Late fetal death rate. Results: Depending on underlying determinants late fetal death rates were greatly increased in extremely small for gestational age fetuses (range 16 to 45 per 1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In extremely small for gestational age fetuses late fetal death rates were increased from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women ⩾175 cm tall. Late fetal death rates were also higher in extremely small for gestational age fetuses in singleton compared with twin pregnancies and in non-hypertensive pregnancies compared with pregnancies complicated by severe pre-eclampsia or other hypertensive disorders. Slightly higher late fetal death rates were observed in nulliparous compared with parous women and in non-smokers compared with smokers.Conclusions: Although the risk of late fetal death is greatly increased in fetuses that are extremely small for gestational age the risk is strongly modified by underlying determinants—for example, there is a lower risk of late fetal death in a small for gestational age fetus if the mother is of short stature, has a twin pregnancy, or has hypertension.

Key messages

• Small for gestational age fetuses are at increased risk of late fetal death regardless of the underlying determinants
• The effect of birthweight ratio on risk of late fetal death is modified by underlying determinants, except maternal age
• Regardless of birthweight ratio the rates of late fetal death are higher among women aged 35 years or older compared with younger women
• In pregnancies of extremely small for gestational age fetuses lower rates of late fetal death are associated with a maternal age of less than 35 years, short maternal stature, multiple births, and hypertensive disorders
• In pregnancies with non-malformed fetuses late fetal death rates are increased in smokers, in multiple births, and in women with severe pre-eclampsia.

     

Plant regeneration from mesophyll protoplasts in Isatis indigotica

Protoplasts of an accession of Isatis indigotica Fort. were isolated from mesophyll tissue by enzymatic digestion and cultured using a feeder cell system. Shoot regeneration efficiency was 100% via organogenesis among 627 isolated calluses within 30–37 days. Among these shoot initiating calluses, 162 (22.6%) developed normal shoots with multiple (2–5) shoots per callus. The remaining calluses developed only vitreous shoots. High concentration (5 μM) of indole-3-butyric acid had a positive effect on rooting compared to low concentration (0.5 μM) of indole-3-butyric acid and α-naphthalene-acetic acid. The average rooting efficiency of regenerated shoots of two experiments was higher on LS medium with 5 μM indole-3-butyric acid than on LS medium without growth regulators. Twenty-nine plantlets, with 2–3 expanded leaves and roots were potted in soil and 22 developed normally to maturity in the glasshouse. This revised version was published online in June 2006 with corrections to the Cover Date.     

Spatio-temporal history of the disjunct family Tecophilaeaceae: a tale involving the colonization of three Mediterranean-type ecosystems

Background and Aims

Tecophilaeaceae (27 species distributed in eight genera) have a disjunct distribution in California, Chile and southern and tropical mainland Africa. Moreover, although the family mainly occurs in arid ecosystems, it has colonized three Mediterranean-type ecosystems. In this study, the spatio-temporal history of the family is examined using DNA sequence data from six plastid regions.

Methods

Modern methods in divergence time estimation (BEAST), diversification (LTT and GeoSSE) and biogeography (LAGRANGE) are applied to infer the evolutionary history of Tecophilaeaceae. To take into account dating and phylogenetic uncertainty, the biogeographical inferences were run over a set of dated Bayesian trees and the analyses were constrained according to palaeogeographical evidence.

Key Results

The analyses showed that the current distribution and diversification of the family were influenced primarily by the break up of Gondwana, separating the family into two main clades, and the establishment of a Mediterranean climate in Chile, coinciding with the radiation of Conanthera. Finally, unlike many other groups, no shifts in diversification rates were observed associated with the dispersals in the Cape region of South Africa.

Conclusions

Although modest in size, Tecophilaeaceae have a complex spatio-temporal history. The family is now most diverse in arid ecosystems in southern Africa, but is expected to have originated in sub-tropical Africa. It has subsequently colonized Mediterranean-type ecosystems in both the Northern and Southern Hemispheres, but well before the onset of the Mediterranean climate in these regions. Only one lineage, genus Conanthera, has apparently diversified to any extent under the impetus of a Mediterranean climate.     

Structure determination of T cell protein-tyrosine phosphatase

Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as a potential drug target in type 2 diabetes. This has in particular been spurred by the finding that PTP1B knockout mice show increased insulin sensitivity and resistance to diet-induced obesity. Surprisingly, the highly homologous T cell protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no x-ray structure has been provided. We have previously co-crystallized PTP1B with a number of low molecular weight inhibitors that inhibit TC-PTP with similar efficiency. Unexpectedly, we were not able to co-crystallize TC-PTP with the same set of inhibitors. This seems to be due to a multimerization process where residues 130-132, the DDQ loop, from one molecule is inserted into the active site of the neighboring molecule, resulting in a continuous string of interacting TC-PTP molecules. Importantly, despite the high degree of functional and structural similarity between TC-PTP and PTP1B, we have been able to identify areas close to the active site that might be addressed to develop selective inhibitors of each enzyme.     

VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy

Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin‐directed AAA‐ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo‐Lysosomal Damage Response. Together, they act downstream of K63‐linked ubiquitination and p62 recruitment, and selectively remove K48‐linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation. Lysosomal clearance is also compromised in MEFs harboring a p97 mutation that causes inclusion body myopathy and neurodegeneration, and damaged lysosomes accumulate in affected patient tissue carrying the mutation. Moreover, we show that p97 helps clear late endosomes/lysosomes ruptured by endocytosed tau fibrils. Thus, our data reveal an important mechanism of how p97 maintains lysosomal homeostasis, and implicate the pathway as a modulator of degenerative diseases.     

Different metabolic responses of human brown adipose tissue to activation by cold and insulin

We investigated the metabolism of human brown adipose tissue (BAT) in healthy subjects by determining its cold-induced and insulin-stimulated glucose uptake and blood flow (perfusion) using positron emission tomography (PET) combined with computed tomography (CT). Second, we assessed gene expression in human BAT and white adipose tissue (WAT). Glucose uptake was induced 12-fold in BAT by cold, accompanied by doubling of perfusion. We found a positive association between whole-body energy expenditure and BAT perfusion. Insulin enhanced glucose uptake 5-fold in BAT independently of its perfusion, while the effect on WAT was weaker. The gene expression level of insulin-sensitive glucose transporter GLUT4 was also higher in BAT as compared to WAT. In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner.     

Environmental and auxin regulation of wood formation involves members of the Aux/IAA gene family in hybrid aspen

Indole acetic acid (IAA/auxin) profoundly affects wood formation but the molecular mechanism of auxin action in this process remains poorly understood. We have cloned cDNAs for eight members of the Aux/IAA gene family from hybrid aspen (Populus tremula L. x Populus tremuloides Michx.) that encode potential mediators of the auxin signal transduction pathway. These genes designated as PttIAA1-PttIAA8 are auxin inducible but differ in their requirement of de novo protein synthesis for auxin induction. The auxin induction of the PttIAA genes is also developmentally controlled as evidenced by the loss of their auxin inducibility during leaf maturation. The PttIAA genes are differentially expressed in the cell types of a developmental gradient comprising the wood-forming tissues. Interestingly, the expression of the PttIAA genes is downregulated during transition of the active cambium into dormancy, a process in which meristematic cells of the cambium lose their sensitivity to auxin. Auxin-regulated developmental reprogramming of wood formation during the induction of tension wood is accompanied by changes in the expression of PttIAA genes. The distinct tissue-specific expression patterns of the auxin inducible PttIAA genes in the cambial region together with the change in expression during dormancy transition and tension wood formation suggest a role for these genes in mediating cambial responses to auxin and xylem development.