Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain

HIV-1 penetration of the brain is a pivotal event in the neuropathogenesis of AIDS-associated dementia. The establishment of productive viral replication or up-regulation of adhesion molecule expression on brain microvascular endothelial cells (BMVEC) could permit entry of HIV into the central nervous system. To investigate the contribution of both, we inoculated primary human BMVEC with high titer macrophage-tropic HIV-1 or cocultured them with virus-infected monocytes. In both instances, BMVEC failed to demonstrate productive viral replication. Cell to cell contact between monocytes and microvascular endothelium resulted in E-selectin expression on BMVEC. BMVEC. cocultured with LPS-activated HIV-infected monocytes expressed even higher levels of E-selectin and vascular cell adhesion molecule-1 (VCAM-1). Transwell assays supported a role of soluble factors, from virus-infected monocytes, for the induction of adhesion molecules on BMVEC. To verify the in vivo relevance of these findings, levels of adhesion molecules were compared with those of proinflammatory cytokines and HIV-1 gene products in brain tissue of AIDS patients with or without encephalitis and HIV-seronegative controls. E-Selectin, and to a lesser degree VCAM-1, paralleled the levels of HIV-1 gene products and proinflammatory cytokines in brain tissue of subjects with encephalitis. Most importantly, an association between macrophage infiltration and increased endothelial cell adhesion molecules was observed in encephalitic brains. Monocyte binding to encephalitic brain tissue was blocked with Abs to VCAM-1 and E-selectin. These data, taken together, suggest that HIV entry into brain is, in part, a consequence of the ability of virus-infected and immune-activated monocytes to induce adhesion molecules on brain endothelium.     

Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane^® and Lipusu^® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.

     

An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heparin Use in Daily Hemodialysis

More frequent dialysis is thought to be associated with increased heparin requirements; however, limited data are available which compare heparin requirements of conventional to daily dialysis. Objectives: To determine differences in heparin dose during conventional thrice‐weekly dialysis (CHD) compared to daily hemodialysis (DHD). Methods: All patients within the daily home hemodialysis at the Northwest Kidney Centers were evaluated for heparin dose both pre‐ and post initiation of daily hemodialysis. Patients on DHD received an initial bolus of heparin, without a continuous heparin drip, and supplemental heparin midway through the dialysis run as needed to maintain adequate activated clotting times (ACTs). CHD patients received a heparin bolus, followed by initiation of heparin drip as needed to maintain adequate ACTs. Results: Of the 1117 patients who dialyze at the NKC, 55% were Caucasian, 21% African‐American, 20% Asian/Pacific Islander, and 35% were of other ethnicity. The majority of patients were greater than 60 years (56%), while 36% ranged from 40–60 years and 13% ranged from 20–40 years. Male patients constituted 54% of patients. Diabetes was the primary cause of renal disease (36%), followed by hypertension (21%) and glomerular disease (18%). Of those patients in the home hemodialysis program (n = 45), 10 patients started daily home hemodialysis using the Aksys daily home hemodialysis system. Of those, the majority was male (100%), Caucasian (78.8%) with an average age of 46.7 ± 18 years. Glomerulonephritis was the primary cause of end‐stage renal disease (40%), while the percentages of other diseases were similar [Alport's syndrome (20%), hypertension (20%) and diabetes (10%)]. Compared to initial DHD heparin requirements (10,111 ± 2219 units), CHD heparin dose requirements (6833 ± 2715 units) were significantly lower (p = 0.045); however, total heparin needs were similar between groups (10,166 ± 4380 units vs. 10,778 ± 2959 units) (p = 0.324). Conclusion: Although patients initiating DHD have greater initial heparin requirements than when on CHD, total heparin doses remain similar to those required on conventional thrice‐weekly hemodialysis. Greater initial heparin doses required during short daily dialysis appear safe compared to those of conventional dialysis.     

Ferroelectric Materials: Probing Local and Global Ferroelectric Phase Stability and Polarization Switching in Ordered Macroporous PZT (Adv. Funct. Mater. 5/2011)

We describe the characterization, ferroelectric phase stability and polarization switching in strain‐free assemblies of PbZr_0.3Ti_0.7O₃ (PZT) nanostructures. The 3‐dimensionally ordered macroporous structures present uniquely large areas and volumes of PZT where the microstructure is spatially modulated and the composition is homogeneous. Variable temperature powder X‐ray diffraction (XRD) studies show that the global structure is crystalline and tetragonal at room temperature and undergoes a reversible tetragonal to cubic phase transition on heating/cooling. The measured phase‐transition temperature is 50–60 °C lower than bulk PZT of the same composition. The local ferroelectric properties were assessed using piezoresponse force spectroscopy that reveal an enhanced piezoresponse from the nanostructured films and demonstrate that the switching polarization can be spatially mapped across these structures. An enhanced piezoresponse is observed in the nanostructured films which we attribute to the formation of strain free films, thus for the first time we are able to assess the effects of crystallite‐size independently of internal stress. Corresponding polarization distributions have been calculated for the bulk and nanostructured materials using a direct variational method and Landau‐Ginzburg‐Devonshire (LGD) theory. By correlating local and global characterization techniques we have for the first time unambiguously demonstrated the formation of tetragonal and ferroelectric PZT in large volume nanostructured architectures. With the wide range of materials available that can be formed into such controlled architectures we conclude that this study opens a pathway for the effective studies of nanoscale ferroelectrics in uniquely large volumes.     

Applications of electron microscopy methods to catalyst problems

The importance of electron microscopy techniques in tackling catalyst problems is considered. In particular the use of the imaging and spectroscopy facilities of the scanning transmission electron microscope is discussed and illustrated with some recent studies of catalytic materials. The advantages of using non-penetrating incident beams in electron-energy-loss spectroscopy, and glancing incidence microscopy, are especially highlighted.Paper presented at the Royal Society-U.S.S.R. Academy of Sciences Workshop, Christ Church, Oxford, April 8–11, 1989.     

International comparison of HV impulse measuring systems

The authors studied the agreement between laboratory measurements of full and front-chopped lightning impulses at four national laboratories. First, some general information on how standards are maintained and disseminated is presented together with a brief review of the requirements for HV impulse measurements. Then, the comparative measurements made in the four national laboratories are presented and the relative differences are reported. Comparative measurements can be made for full standard lightning impulses to within 1% for crest voltages and to within 5% for front times. These uncertainties may be adequate to allow the calibration of industrial measuring systems to within 3% for crest values and 10% for front times, as is required by the relevant standards, provided the systematic errors of the reference system are sufficiently small     

Secondary alveolar bone grafting--five-year periodontal and radiographic evaluation in 100 consecutive cases

A prospective study of secondary alveolar bone grafting based on the Norwegian (Oslo) team approach has been conducted by the CLP Unit at the Princess Margaret Hospital for Children in Perth, Australia, since 1982. The 5-year results of 100 consecutive cases of uni- and bilateral cases are presented according to periodontal and radiographic parameters of tooth support. The vast majority of cases grafted (98%) resulted in the eventual eruption of the cleft side cuspid/lateral incisor within acceptable parameters of tooth support. The results confirm the predictability of this safe procedure when utilized within a strict clinical protocol involving the whole CLP team.