Apolipoprotein B mRNA editing and apolipoprotein gene expression in the liver of hyperinsulinemic fatty zucker rats: Relationship to very low density lipoprotein composition

We previously demonstrated increased apolipoprotein B (apoB) mRNA editing, elevated levels of mRNA for the catalytic component of the apoB mRNA editing complex, apobec-1, and increased secretion of the product of the edited mRNA, apoB48, in very low density lipoproteins (VLDL) in primary cultures of Sprague-Dawley rat hepatocytes following insulin treatment. In order to determine the effect of in vivo hyperinsulinemia on these processes, we determined apoB mRNA editing, apobec-1 expression, hepatic expression of mRNA for apoB and other VLDL apoproteins, and the quantity and composition of plasma VLDL in the hyperinsulinemic fatty Zucker rat. Total apoB mRNA content of the livers of the fatty rats and lean littermates did not differ, however, edited apoB message coding for hepatic apo B48, and abundance of mRNA for the catalytic subunit of the apoB mRNA editing complex, apobec-1, was increased by 1.7-and 3.3-fold, respectively, in fatty rats. ApoCIII mRNA abundance was increased in livers of fatty rats as well, but the abundance of hepatic apoE mRNA in the fatty animal was not different from that of the lean rat. Hepatic apoAI mRNA abundance was also increased in the fatty rats. Associated with increased apoB mRNA editing, was the 1.7-fold increase in the fraction of apoB in plasma as apoB48 in fatty rats. VLDL-triglyceride and-apoB in plasma were 15-and 3-fold higher, respectively, in fatty Zucker rats compared to lean littermates, indicating both enrichment of VLDL with triglycerides and increased accumulation of VLDL particles. Increased hepatic expression of mRNA for apoCIII and apoAI was associated with increased content of apoC (and relative depletion of apoE) in VLDL of fatty rats, and plasma apoAI was increased in fatty Zucker rats, primarily in the HDL fraction. The current study provides further evidence that chronic exposure to high levels of insulin influences both the quantity of and lipid/apoprotein composition of VLDL in plasma. The increased apoC and decreased apoE (as well as increased triglyceride) content of VLDL in the fatty Zucker rat observed in the current study may affect VLDL clearance and therefore may be a factor in the observed accumulation of VLDL in the plasma of the fatty hyperinsulinemic Zucker rats.     

Hydrodynamics of three-phase fluidized bed systems examined by statistical, fractal, chaos and wavelet analysis methods

Hydrodynamic studies were conducted in gas-liquid-solid systems (0.1 m ID, 2 m high) of 3.0 mm glass beads and of 2.1 mm polypropylene low-density particles, with particles densities of 2471 and 1290 kg/m³, respectively. Simultaneous measurement of differential pressure and bubble conductivity probe signals sampled at 500 Hz for 60 s enabled the investigation of the change in flow structure in relation to the flow regime transitions. Superficial gas velocities ranged between 0.010 and 0.052 m/s for polypropylene particles, and extended to 0.12 m/s for glass beads, while the superficial liquid velocities covered the ranges of 0.0007-0.045 m/s for polypropylene particles, and ranged up to 0.056 m/s for glass beads.Spectral analysis of the pressure fluctuations revealed a transition from dispersed to coalesced bubbling flow with decreasing liquid velocity for a given superficial gas velocity. The use of a conductivity probe facilitated characterization of the local flow structure in terms of bubble movement. The measurements were extensively analyzed using fractals and chaos, power spectra frequency analysis and wavelet decomposition in addition to the standard statistical analyses. The coefficient of variation of the bubble probe signals was found to be the most effective in deducing the transition velocity between coalesced and dispersed bubbling flow regimes, while wavelet energy confirmed the similarity in the distribution between two axial positions once operated in the dispersed flow regime. Comparison of the flow structure between glass beads and polypropylene particles showed that both the minimum liquid fluidization velocity and the transition velocity between the bubble flow regimes were much higher for the glass beads than for the lighter polypropylene particles. Furthermore, the standard deviations of the decomposed bubble probe signals through wavelet transformation successfully highlighted the difference between the two systems of particles.     

Community Participation in Urban Planning: the Case of Managing Green Spaces in Kumasi,Ghana

The entrenched position now taken by participatory planning in urban planning practice has made the call for community participation in the planning process now higher than ever. Community participation has been well-acknowledged to give local people a voice in planning decisions. This paper assessed the level of participation by local people in the management of urban green spaces. Using a case study research approach, Kumasi city, once the garden city of Africa was selected as the study area. The Kumasi city authorities, and residents including opinion leaders, and officials of allied bodies on green spaces constituted the study’s target population. A blend of qualitative research techniques such as in-depth interviews, focus group discussion, and personal observation was employed whilst theoretical sampling technique was adopted. It was found out that the participation of the local people in the management of green space was low. The local people were neither consulted nor informed on green space projects (parks and gardens) by the city authorities. They were also not empowered to self-facilitate initiatives on green spaces and passively involved in final decisions on green spaces. To correct the situation, it is recommended that features of the communicative planning theory such as dialogue, consensus building, and facilitative leadership should be given attention in the urban planning system of Kumasi especially on green space projects.     

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice

The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1^−/−) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1^−/− mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1^−/− and wild type mice. GC1^−/− mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1^−/− mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1^−/− mice.     

Optimal liquid acquisition device screen weave for a liquid hydrogen fuel depot

This paper presents the rationale for choosing the optimal screen type for a fully robust screen channel liquid acquisition device (LAD) to be implemented into future in-space liquid hydrogen (LH₂) fuel depots. Typical Dutch Twill, Plain Dutch, Twilled Square, and Plain Square weaves are initially considered for comparison. From the set of influential performance parameters from Hartwig and Darr [1], bubble point pressure and flow-through-screen (FTS) pressure drop are combined to define a critical mass flux used to make general comparisons between screens. Based off the minimum bubble point pressure to maintain adequate phase separation against adverse depot acceleration levels, the five finest Dutch Twill screens are down selected for the depot. Along with secondary parameters such as wicking rate and screen compliance, a minimum screen area is defined to select the optimal mesh. Results here indicate that the 450 × 2750 Dutch Twill mesh may be the optimal screen weave for a future LH₂ fuel depot.     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Poly(cyclodextrin)‐Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

Despite the approval of oncolytic virus (OV) therapy for advanced melanoma, its intrinsic limitations that include the risk of persistent viral infection and cost‐intensive manufacturing motivate the development of analogous approaches that are free from the disadvantages of virus‐based therapies. Herein, reported is a nanoassembly comprised of multivalent host–guest interactions between polymerized paclitaxel (pPTX) and nitric oxide‐incorporated polymerized β‐cyclodextrin (pCD‐pSNO) that through its bioactive components and when used locoregionally recapitulates the therapeutic effects of OV. The resultant pPTX/pCD‐pSNO exhibits significantly enhanced cytotoxicity, immunogenic cell death, dendritic cell (DC) activation, and T cell expansion in vitro compared to free agents alone or in combination. In vivo, intratumoral administration of pPTX/pCD‐pSNO results in activation and expansion of DCs systemically, but with a corresponding expansion of myeloid‐derived suppressor cells and suppression of CD8⁺ T cell expansion. When combined with antibody targeting cytotoxic T lymphocyte antigen‐4 that blunts this molecule's signaling effects on T cells, intratumoral pPTX/pCD‐pSNO treatment elicits potent anticancer effects that significantly prolong animal survival. This formulation thus leverages the chemo‐ and immunotherapeutic synergies of PTX and nitric oxide and suggests the potential for virus‐free nanoformulations to mimic the therapeutic action and benefits of OVs.     

Impact of air‐handling system exhaust failure on dissemination pattern of simulant pathogen particles in a clinical biocontainment unit

Biocontainment units (BCUs) are facilities used to care for patients with highly infectious diseases. However, there is limited guidance on BCU protocols and design. This study presents the first investigation of how HVAC (heating, ventilation, air‐conditioning) operating conditions influence the dissemination of fluorescent tracer particles released in a BCU. Test conditions included normal HVAC operation and exhaust failure resulting in loss of negative pressure. A suspension of optical brightener powder and water was nebulized to produce fluorescent particles simulating droplet nuclei (0.5‐5 μm). Airborne particle number concentrations were monitored by Instantaneous Biological Analyzers and Collectors (FLIR Systems). During normal HVAC operation, fluorescent tracer particles were contained in the isolation room (average concentration = 1 × 10⁴ ± 3 × 10³/L_air). Under exhaust failure, the automated HVAC system maximizes airflow into areas adjacent to isolation rooms to attempt to maintain negative pressure differential. However, 6% of the fluorescent particles were transported through cracks around doors/door handles out of the isolation room via airflow alone and not by movement of personnel or doors. Overall, this study provides a systematic method for evaluating capabilities to contain aerosolized particles during various HVAC scenarios. Recommendations are provided to improve situation‐specific BCU safety.     

Apple quality,storage, and washing treatments affect patulin levels in apple cider

Patulin is a mycotoxin produced primarily by Penicillium expansum, a mold responsible for rot in apples and other fruits. The growth of this fungus and the production of patulin are common in fruit that has been damaged. However, patulin can be detected in visibly sound fruit. The purpose of this project was to determine how apple quality, storage, and washing treatments affect patulin levels in apple cider. Patulin was not detected in cider pressed from fresh tree-picked apples (seven cultivars) but was found at levels of 40.2 to 374 microg/liter in cider pressed from four cultivars of fresh ground-harvested (dropped) apples. Patulin was not detected in cider pressed from culled tree-picked apples stored for 4 to 6 weeks at 0 to 2 degrees C but was found at levels of 0.97 to 64.0 microg/liter in cider pressed from unculled fruit stored under the same conditions. Cider from controlled-atmosphere-stored apples that were culled before pressing contained 0 to 15.1 microg of patulin per liter, while cider made from unculled fruit contained 59.9 to 120.5 microg of patulin per liter. The washing of ground-harvested apples before pressing reduced patulin levels in cider by 10 to 100%, depending on the initial patulin levels and the type of wash solution used. These results indicate that patulin is a good indicator of the quality of the apples used to manufacture cider. The avoidance of ground-harvested apples and the careful culling of apples before pressing are good methods for reducing patulin levels in cider.