Is there a gloxylate cycle in the liver of the fetal guinea pig?

Studies on the effect of the inhibitor of fatty acid oxidation (+)-octanoylcarnitine on the perfused liver of the 48–51 days fetal guinea pig indicate that the oxidation of endogenous fatty acids is a major source of carbon for the citric acid cycle and for synthesis of hexose. Consistent with this the liver can convert isocitrate to glyoxylate and glyoxylate to malate and may therefore operate a glyoxylate cycle allowing the net production of sugars from acetyl-CoA.     

Transforming growth factor β3 in the fetal and neonatal rat testis: immunolocalization and effect on fetal Leydig cell function

The localization of transforming growth factor β3 (TGFβ3) in the fetal and neonatal testis (from fetal day 13.5 to postnatal day 6) was investigated by immunohistochemical staining with a specific polyclonal antibody raised against a synthetic peptide corresponding to residues 50–75 of TGFβ3. This antibody recognized 0.5 ng TGFβ3 in western blot analysis, but did not detect 25 ng TGFβ1 or TGFβ2. The immunolocalization of TGFβ3 in the fetal and neonatal testis changed throughout development. Immunostaining was present in the gonocytes by fetal day 13.5, persisted until postnatal day 3, and was heterogeneous in spermatogonia on postnatal day 6. The Sertoli cells contained no immunoreactivity at any age. The fetal-type Leydig cells were first immunostained for TGFβ3 on day 16.5 and staining became very intense from day 18.5 onward. Staining disappeared when the antibody was presaturated with the synthetic peptide, but persisted when the antibody was presaturated with a tenfold excess of the corresponding peptide from TGFβ2. Furthermore, we researched whether TGFβ3 could act as a local regulator of fetal Leydig cell function. In a dispersed fetal testicular cell system, TGFβ3 inhibited the LH-stimulated testosterone production by Leydig cells from 20.5-day-old fetuses. The inhibitory effect of TGFβ3 was equal to that observed with TGFβ1 or TGFβ2. When compared with our previous studies showing the immunolocalization of TGFβ1 and TGFβ2, the present study shows that TGFβ3 may have a specific role in the developing rat testis, but may also overlap the action of TGFβ1 and TGFβ2. Accepted: 8 June 1999     

Is transdifferentiation in trouble?

Spectacular examples of transdifferentiation—such as brain cells turning to blood and blood to brain—have given way to sneaking suspicions about artifacts in culture, fusion, and clonality. Could cell fates be relatively fixed after all?The exact fate map of Caenorhabditis elegans is a dream for developmental biology control freaks. Stem cells, which can both self-renew and produce a particular set of differentiated progeny, seemed like the mammalian equivalent, albeit a little more malleable and messy.But lately this view of development as a controlled series of fate maps, with each cell type performing one and only one function, has come under attack. Stem cell researchers have claimed that brain can be turned into blood (Bjornson et al., 1999), and blood into brain (Brazelton et al., 2000; Mezey et al., 2000; Priller et al., 2001), muscle (Ferrari et al., 1998), myocardium (Orlic et al., 2001) or liver (Lagasse et al., 2000). In the hands of some investigators, bone marrow (Krause et al., 2001) and neural stem cells (Clarke et al., 2000) can apparently turn into pretty much everything.“I believe this phenomenon was missed for a very long time,” says Helen Blau (Stanford University, Stanford, CA), “because we didn''t have the imagination to think that it could happen or the tools to prove it.” The orgy of plasticity has prompted Blau to propose a new way of thinking about cell fate determination (Blau et al., 2001), with stem cell capability existing as a switch that can be turned on and altered as easily as an apoptotic program.But others see at least some of the reports of cell fate changes—also known as transdifferentiation—as simply sloppy science. “The emphasis,” says Sean Morrison (University of Michigan, Ann Arbor, MI), “has been on describing spectacular results rather than on describing it in an evenhanded way that would identify the real importance of the phenomenon.” Several dissenters have called for more stringent criteria for judging transdifferentiation experiments (Anderson, 2001; Anderson et al., 2001).As follow-up studies emerge, questions have been raised about some of the earlier results. The verdict is not in yet, but the resolution of this debate will have implications on several fronts, determining our view of basic stem cell biology, affecting the strategy for treating patients with stem cell therapies, and influencing the steps used by the United States Congress to regulate stem cell research.     

Osteogenic PTHs and vascular ossification—Is there a danger for osteoporotics?

Inflammation in vascular (mostly arterial) walls and heart valves triggered by the trans-endothelial influx of LDL particles and the action of subsequently modified (e.g., by oxidation) LDL particles can trigger true bone formation by valvar fibroblasts, by a subpopulation of re-differentiation-competent VSMCs (vascular smooth muscle cells) or by vascular pericytes. Vascular ossification can lead to heart failure and death. Elderly osteoporotic women who need osteogenic drugs to restore their lost skeletal bone are paradoxically prone to vascular ossification-the "calcification paradox." The recent introduction into the clinic of a potently osteogenic parathyroid hormone peptide, Lilly's rhPTH-(1-34)OH (Forteotrade mark), to reverse skeletal bone loss raises the question of whether this and other potently osteogenic PTHs still in clinical trial might also stimulate vascular ossification in such osteoporotic women. Indeed the VSMCs in human and rat atherosclerotic lesions hyperexpress PTHrP and the PTHR1 (or PTH1R) receptor as do maturing osteoblasts. And the evidence indicates that endogenous PTHrP with its NLS (nuclear/nucleolar localization sequence) does stimulate VSMC proliferation (a prime prerequisite for atheroma formation and ossification) via intranuclear targets that inactivate pRb, the inhibitory G1/S checkpoint regulator, by stimulating its hyperphosphorylation. But neither externally added full-length PTHrP nor the NLS-lacking PTHrP-(1-34)OH gets into the VSMC nucleus and instead they inhibit proliferation and calcification by only activating the cell's PTHR1 receptors. No PTH has an NLS and, as expected from the observations on the externally added PTHrPs, hPTH-(1-34)OH inhibits calcification by VSMCs and cannot stimulate vascular ossification in a diabetic mouse model. Encouraging though this may be for osteoporotics with their "calcification paradox," more work is needed to be sure that the skeletally osteogenic PTHs do not promote vascular ossification with its cardiovascular consequences.     

Is fetal heart rate monitoring sufficiently sensitive to detect changes during labour?

Although fetal monitoring is a common clinical procedure, there is little quantitative evidence that it can detect changes occurring during labour. We present quantitative data comparing the first and second stage of labour, from 21 labours resulting in a normal fetal outcome. A range of fetal heart rate variables was calculated from the output of a fetal heart rate monitor. Significant changes were detected in baseline fetal heart rate (P < 0.005), heart rate variability (P < 0.05), number of dips (P < 0.01).and their depth (P < 0.01). The results encourage confidence in the sensitivity of fetal monitoring for the detection of changes in a number of fetal heart rate variables during the course of labour.     

Is mucus involved in biocrystallization?

Summary Freeze-dried intestinal mucus of sea-water-adapted eels was analysed by scanning electron microscopy (SEM) and X-ray microanalysis. Calcite crystals were observed in the mucus fibres; their concentration increased along the hindgut. Random SEM observations made in situ indicated that mucus fibres were involved in the genesis of these crystals. Calcium-rich mucus globules were found fused inside crystal matrices. Single typical rhombohedric crystals of various complexity appeared within the mucus framework. The steps of crystal biogenesis were reconstituted in in-vitro conditions.     

Ghrelin and obestatin: different role in fetal lung development?

Ghrelin and obestatin are two proteins that originate from post-translational processing of the preproghrelin peptide. Various authors claim an opposed role of ghrelin and obestatin in several systems. Preproghrelin mRNA is significantly expressed in airway epithelium throughout lung development, predominantly during the earliest stages. The aim of this study was to evaluate the role of ghrelin and obestatin in fetal lung development in vitro. Immunohistochemistry studies were performed at different gestational ages in order to clarify the expression pattern of ghrelin, GHS-R1a, obestatin and GPR39 during fetal lung development. Fetal rat lung explants were harvested at 13.5 days post-conception (dpc) and cultured during 4 days with increasing doses of total ghrelin, acylated ghrelin, desacyl-ghrelin, ghrelin antagonist (D-Lys(3)-GHRP-6) or obestatin. Immunohistochemistry studies demonstrated that ghrelin, GHS-R1a, obestatin and GPR39 proteins were expressed in primitive rat lung epithelium throughout all studied gestational ages. Total and acylated ghrelin supplementation significantly increased the total number of peripheral airway buds, whereas desacyl-ghrelin induced no effect. Moreover, GHS-R1a antagonist significantly decreased lung branching. Finally, obestatin supplementation induced no significant effect in the measured parameters. The present study showed that ghrelin has a positive effect in fetal lung development through its GHS-R1a receptor, whereas obestatin has no effect on lung branching.     

Is energy deficiency good in moderation?

In this issue, Pospisilik et al. (2007) demonstrate that a reduction in mitochondrial oxidative phosphorylation protects mice against obesity and diabetes. This finding suggests that the moderate deficiency in oxidative phosphorylation that is observed in peripheral tissues of insulin-resistant humans is not a causative factor in diabetes but may instead be a compensatory response.     

Is there chaos in plankton dynamics?

A controversial issue in ecosystem modeling is whether the irregularfluctuations that one observes in nature are due solely to randomenvironmental factors or whether, at least partially, a deterministicmechanism is responsible for the unpredictable behavior. Thissecond alternative is called deterministic chaos and the issuein this paper is to decide if actual plankton time series canvindicate the hypothesis of chaotic dynamics. The near-neighborforecasting method is a recent technique for detecting determinismin a time series and we apply it to measurements of phytoplanktonand zooplankton biomass obtained at a single station in theMiddle Atlantic Bight. Although the results do not concludethe presence of chaos, they do give some support to the ideathat deterministic non-linear trophic dynamics may account forat least some of the variability that is seen in the data, particularlyin terms of inferring zooplankton oscillations from those ofphytoplankton.