The in vivo actions of insulin-like growth factor-I (IGF-I) on prenatal and early postnatal brain development were investigated in transgenic (Tg) mice that overexpress IGF-I prenatally under the control of regulatory sequences from the nestin gene. Tg mice demonstrated increases in brain weight of 6% by embryonic day (E) 18 and 27% by postnatal day (P) 12. In Tg embryos at E16, the volume of the cortical plate was significantly increased by 52% and total cell number was increased by 54%. S-phase labeling with 5-bromo-2'-deoxyuridine revealed a 13-15% increase in the proportion of labeled neuroepithelial cells in Tg embryos at E14. In Tg mice at P12, significant increases in regional tissue volumes were detected in the cerebral cortex (29%), subcortical white matter (52%), caudate-putamen (37%), hippocampus (49%), dentate gyrus (71%) and habenular complex (48%). Tg mice exhibited significant increases in the total number of neurons in the cerebral cortex (27%), caudate-putamen (27%), dentate gyrus (69%), medial habenular nucleus (61%) and lateral habenular nucleus (36%). In the cerebral cortex and subcortical white matter of Tg mice, the total numbers of glial cells were significantly increased by 37% and 42%, respectively. The numerical density of apoptotic cells in the cerebral cortex, labeled by antibodies against active caspase-3, was reduced by 26% in Tg mice at P7. Our results demonstrate that IGF-I can both promote proliferation of neural cells in the embryonic central nervous system in vivo and inhibit their apoptosis during postnatal life.

Microglia are the resident immune cell of the central nervous system (CNS), and serve to protect and maintain the local brain environment. Microglia are critically dependent on signaling through the colony-stimulating factor 1 receptor (CSF1R); administration of CSF1R inhibitors that cross the blood brain barrier (BBB) lead to the elimination of up to 99% of microglia, depending on CNS exposure and treatment duration. Once microglia are depleted, withdrawal of inhibitor stimulates repopulation of the entire CNS with new cells, conceivably enabling a therapeutic strategy for beneficial renewal of the entire microglial tissue. We have explored the kinetics and limits of this repopulation event and show that the rate of microglial repopulation is proportional to the extent of microglial depletion – greater depletion of microglia results in more rapid repopulation. Using a CSF1R inhibitor formulation that eliminates ~99% of microglia within 7 days, we subjected mice to multiple rounds of elimination (7 days’ treatment) and repopulation (7 days’ recovery) and found that the brain only has the capacity for a single complete repopulation event; subsequent elimination and CSF1R inhibitor withdrawal fail to repopulate the brain. However, if the recovery time between, or after, cycles is extended sufficiently then the brain can ultimately repopulate. These kinetic studies define the opportunities and possible limits of the remarkable renewal capacities of microglia.

The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.

Cells of the monocyte-macrophage series must carry out discrete accessory-cell functions during the process of antigen-specific T-cell activation. One of these functions is the cell-surface expression of major histocompatibility complex (MHC) class II gene products, which are involved in the presentation of foreign antigen to T cells. Previously, we reported that murine peritoneal macrophages infected with the obligate intracellular protozoan Leishmania donovani had suppressed responses to y interferon (IUFN-y) for the induction ofMHC class II antigen expression. To determine the molecular basis for this suppression, we examined in the present series of experiments the interaction of this organism with cells of the murine macrophage tumor cell line P388D1.

Nucleation from a supercooled melt of palm oil was studied by optical microscopy and differential scanning calorimetry (DSC}. Despite being a multicomponent system, palm oil exhibits a rather simple cooling thermogram with its high-and low-T cxotherms exclusively related to the "hard" and "soft" components of the oil. As the "hard" components are being removed, the position of the high-T peak shifts down toward the low-T peak with diminishing peak intensity, while the position of the latter remains virtually unchanged.At 288~ nucleation in a palm oil melt is instantaneous. Its induction time-temperature curve shows an abrupt discontinuity at 297~ which demarcates the occurrence of one polymorph from another. Nucleation data fit very well into the Fisher-Turnbull equation. Its larger activation free energy of nucleation is accompanied by lowering of the melting point and an increase in the crystal/melt interracial free energy as compared to palm stearin. The slow rate of nucleation in palm oil is attributed to intermolecular interaction between its "hard" and "soft" components.

Isothermal crystallization of palm oil was studied by means of differential scanning calorimetry (DSC) as well as by nuclear magnetic resonance spectrometry to monitor its solid fat content (SFC). The temperature of crystallization (Tc) varied from 0 to 30~ depending on the method used. The plot of %SFC vs. time at 25~ was sigmoidal in shape. However, at lower temperatures, two consecutive curves were clearly visible. Results from DSC experiments showed the following interesting features. At each Tc, the crystals produced were of different compositions. From 0 to 8~ the thermogram showed three peaks, with the first two peaks (I and II) sharp, and the third (III) rather broad. At elevated temperatures up to 20~ peak II disappeared totally while peak III tended to shift toward peak I. Above 20~ both peaks shifted downward to longer times. Peak I continued to be broadened, and then suddenly disappeared at Tc above 24~ The melting thermograms of the crystals obtained above and below this cutmff point were distinctly different. Kinetic studies on isothermal crystallization based on the data of SFC measurements showed that the data fit well into the Avrami-Erofeev equation with n = 3 over the first 70% of the crystallization.

Cytokines produced by mononuclear cells are important regulatory and effector molecules and evidence has been presented to support a role at least for tumor necrosis factor-a (TNF-a) and interferon-y (IFN-y) in host defense against Leishmania.

The foundation of solid state decomposition kinetics is based on the well known theory of nucleation and nucleus growth put forward by Jacobs and Tompkins. It has now been shown that all the kinetic equations thus derived can be represented by a general differential form: ������������������������� dα/dt = kα1-p(1-α)1-q in which α, t and k are respectively the fractional decomposition, time and rate constant; while p and q are parameters lying between zero and unity inclusively. A method has been suggested to find p and q experimentally, thereby enabling one to find the appropriate kinetic form for the chemical decomposition. The conventional method involves the testing of various existing equations to the decomposition data. Different equations are found to fit over different ranges of the decomposition curve so that it is difficult to decide which is the correct kinetic equation for a particular reaction. The present approach however eliminates this complication.