Human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line)

hUCB‐MSC (human umbilical cord blood‐derived mesenchymal stem cells) offer an attractive alternative to bone marrow‐derived MSC for cell‐based therapy by being less invasive a source of biological material. We have evaluated the effect of hUCB‐MSC on the proliferation of K562 (an erythromyeloblastoid cell line) and the cytokine secretion pattern of hUCB‐MSC. Co‐culturing of hUCB‐MSC and K562 resulted in inhibition of proliferation of K562 in a dose‐dependent manner. However, the anti‐proliferative effect was reduced in transwells, suggesting the importance of direct cell‐to‐cell contact. hUCB‐MSC inhibited proliferation of K562, arresting them in the G₀/G₁ phase. NO (nitric oxide) was not involved in the hUCB‐MSC‐mediated tumour suppression. The presence of IL‐6 (interleukin 6) and IL‐8 were obvious in the hUCB‐MSC conditioned media, but no significant increase was found in 29 other cytokines. Th1 cytokines, IFNα (interferon α), Th2 cytokine IL‐4 and Th17 cytokine, IL‐17 were not secreted by hUCB‐MSC. There was an increase in the number of hUCB‐MSC expressing the latent membrane‐bound form of TGFβ1 co‐cultured with K562. The anti‐proliferative effect of hUCB‐MSC was due to arrest of the growth of K562 in the G₀/G₁ phase. The mechanisms underlying increased IL‐6 and IL‐8 secretion and LAP (latency‐associated peptide; TGFβ1) by hUCB‐MSC remains unknown.     

Terminal end bud maintenance in mammary gland is dependent upon FGFR2b signaling

We previously demonstrated that Fibroblast Growth Factor 10 (FGF10) and its receptor FGFR2b play a key role in controlling the very early stages of mammary gland development during embryogenesis [Mailleux, A.A., Spencer-Dene, B., Dillon, C., Ndiaye, D., Savona-Baron, C., Itoh, N., Kato, S., Dickson, C., Thiery, J.P., and Bellusci, S. (2002). Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development 129, 53-60. Veltmaat, J. M., Relaix, F., Le, L.T., Kratochwil, K., Sala, F.G., van Veelen, W., Rice, R., Spencer-Dene, B., Mailleux, A.A., Rice, D.P., Thiery, J.P., and Bellusci, S. (2006). Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes. Development 133, 2325-35.]. However, the role of FGFR2b signaling in postnatal mammary gland development is still elusive. We show that FGF10 is expressed at high level throughout the adipose tissue in the mammary gland of young virgin female mice whereas its main receptor FGFR2 is found mostly in the epithelium. Using a rtTA transactivator/tetracycline promoter approach allowing inducible and reversible attenuation of the FGFR2b signaling throughout the adult mouse, we are now reporting that FGFR2b signaling is also critical during postnatal mammary gland development. Ubiquitous attenuation of FGFR2b signaling in the postnatal mouse for 6 weeks starting immediately after birth is not lethal and leads to minor defects in the animal. Upon dissection of the mammary glands, a 40% reduction in size compared to the WT control is observed. Further examination shows a rudimentary mammary epithelial tree with completely absent terminal end buds (TEBs), compared to a well-branched structure observed in wild type. Transplantation of mammary gland explants into cleared fat pad of wild type mouse recipients indicates that the observed abnormal branching results from defective FGFR2b signaling in the epithelium. We also demonstrate that this rudimentary tree reforms TEBs and resumes branching upon removal of doxycycline suggesting that the regenerative capacities of the mammary epithelial progenitor cells were still functional despite long-term inactivation of the FGFR2b pathway. At the cellular level, upon FGFR2b attenuation, we show an increase in apoptosis associated with a decrease in the proliferation of the mammary luminal epithelium. We conclude that during puberty, there is a differential requirement for FGFR2b signaling in ductal vs. TEBs epithelium. FGFR2b signaling is crucial for the survival and proliferation of the mammary luminal epithelial cells, but does not affect the regenerative potential of the mammary epithelial progenitor cells.     

Antibacterial activity of three South Indian seagrasses, <Emphasis Type="Italic">Cymodocea serrulata</Emphasis>, <Emphasis Type="Italic">Halophila ovalis</Emphasis> and <Emphasis Type="Italic">Zostera capensis</Emphasis>

The antibacterial properties of the three seagrasses namely Cymodocea serrulata, Halophila ovalis and Zostera capensis were tested against the human pathogens Staphylococcus aureus, Bacillus cereus, B. subtilis, Escherichia coli, Salmonella paratyphi, Salmonella typhimurium and Micrococcus luteus, using six different solvents namely, petroleum ether, chloroform, ethyl acetate, acetone, methanol and water. Ethyl acetate and methanol extracts showed maximum activity against most of the pathogens when compared to other solvents. Experiments are underway to isolate active compound(s) implicated in controlling the growth of the pathogens in vitro.     

Pathology of the male baboon (Papio spp.) urogenital system

Background Comprehensive reports on male baboon urogenital pathology are not available. Methods We performed a retrospective study of 2246 male baboon necropsy records over 19 years. Results A total of 289 urogenital lesions were diagnosed in 197 (8.8%) baboons. The most frequently affected organs in decreasing order were kidney, testicle, urinary bladder, penis and prepuce, seminal vesicle, ureter, and prostate. Lesions were rare in the urethra, scrotum, and epididymis. The most common diagnoses in decreasing order were nephritis, urinary bladder cystitis, nephrocalcinosis, pyelonephritis, renal cysts, renal amyloidosis, testicular atrophy, penile/preputial dermatitis, hydronephrosis, orchitis/testicular abscess, glomerulonephritis, renal hemorrhage, hypospadia, nephrosis, renal infarct, hypospermia/aspermia, seminal vesicle mineralization, and hydroureter. We also report six cases of hypospadia, the first report in the baboon. Conclusions The male baboon has a low incidence of urogenital disease and renal disease is the most common malady. The role of herpesvirus papio 2 needs further study.     

Optimization of <Emphasis Type="Italic">Enterobacter cloacae</Emphasis> (KU923381) for diesel oil degradation using response surface methodology (RSM)

Efficiency of Enterobacter cloacae KU923381 isolated from petroleum hydrocarbon contaminated soil was evaluated in batch culture and bioreactor mode. The isolate were screened for biofilm formation using qualitative and quantitative assays. Response surface methodology (RSM) was used to study the effect of pH, temperature, glucose concentration, and sodium chloride on diesel degradation. The predicted values for diesel oil degradation efficiency by the statistical designs are in a close agreement with experimental data (R ² = 99.66%). Degradation efficiency is increased by 36.78% at pH = 7, temperature = 35°C, glucose = 5%, and sodium chloride concentration = 5%. Under the optimized conditions, the experiments were performed for diesel oil degradation by gas chromatographic mass spectrometric analysis (GC-MS). GC-MS analysis confirmed that E. cloacae had highly degrade hexadecane, heptadecane, tridecane, and docosane by 99.71%, 99.23%, 99.66%, and 98.34% respectively. This study shows that rapid bioremoval of hydrocarbons in diesel oil is acheived by E. cloacae with abet of biofilm formation. The potential use of the biofilms for preparing trickling filters (gravel particles) for the degradation of hydrocarbons from petroleum wastes before their disposal in the open environment is highly suggested. This is the first successful attempt for artificially establishing petroleum hydrocarbon degrading bacterial biofilm on solid substrates in bioreactor.     

The parasitic fly Nemorilla maculosa exploits host‐plant volatiles to locate the legume pod borer,Maruca vitrata

Nemorilla maculosa Meigen (Diptera: Tachinidae) is a solitary endoparasitoid of the legume pod borer, Maruca vitrata Fabricius (Lepidoptera: Crambidae), a key pest of cowpea, Vigna unguiculata (L.) Walp. (Fabaceae) in Africa. A colony of N. maculosa, introduced for experimental purposes from Taiwan to the laboratories of the International Institute of Tropical Agriculture (IITA) in Benin, was used for our studies. Olfactory reponses of N. maculosa to leaves of infested or uninfested cowpea and yellow peabush, Sesbania cannabina (Retz.) Pers. (Fabaceae), and to M. vitrata larvae were evaluated in a four‐arm olfactometer. For all combinations of odor sources, responses between naïve and oviposition‐experienced female flies did not differ. Nemorilla maculosa females were attracted by odors from uninfested leaves of yellow peabush and flowers of cowpea when compared with clean air, and they were attracted to plants damaged by M. vitrata with larvae removed. However, the female fly did not discriminate between odors from infested and uninfested plants. The parasitic fly N. maculosa proved well able to use volatile compounds from various host plants (peabush and cowpea) to locate its host, with a more pronounced attraction by the combination of host larvae and infested host plant parts. These findings are discussed in light of the prospective use of N. maculosa as a biological control agent against the legume pod borer.     

Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs

Double relapsed and/or refractory multiple myeloma (DRMM), MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU) costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was £23,472 [range: £1,411–£90,262], split between drug costs £11,191 and other resource use costs £12,281. The cost per assumed quality-adjusted life year (QALY) during DRMM was £66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM.     

Amino Acid Nucleic Acids: Synthesis and Hybridization Properties of a Novel Class of Antisense Oligonucleotides

Abstract

Oligonucleotides containing novel phoshoramidite 12 were synthesized and studied for their hybridization properties for the first time. Interestingly, these modified oligonucleotides showed a remarkable resistance to exonuclease.     

Glia Maturation Factor Expression in Entorhinal Cortex of Alzheimer’s Disease Brain

Alzheimer’s disease (AD) is characterized by the presence of neuropathological lesions containing amyloid plaques (APs) and hyperphosphorylated Tau containing neurofibrillary tangles (NFTs) and is associated with neuroinflammation and neurodegeneration. Entorhinal cortex (Brodmann’s area 28) is involved in memory associated functions and is one of the first brain areas targeted to form the neuropathological lesions and also severely affected cortical region in AD. Glia maturation factor (GMF), a central nervous system protein and a proinflammatory molecule is known to be up-regulated in the specific areas of AD brain. Our previous immunohistochemical studies using temporal cortex showed that GMF is expressed in the vicinity of APs and NFTs in AD brains. In the present study, we have analyzed the expression of GMF and its association with APs and NFTs in the entorhinal cortex of AD brains by using immunohistochemistry combined with thioflavin-S fluorescence labeling methods. Results showed that GMF immunoreactive glial cells, glial fibrillary acidic protein labeled reactive astrocytes and ionized calcium binding adaptor molecule-1 labeled activated microglia were increased in the entorhinal cortical layers especially at the sites of 6E10 labeled APs and Tau containing NFTs. In conclusion, increased expression of GMF by the glial cells in the entorhinal cortex region, and the co-localization of GMF with APs and NFTs suggest that GMF may play important proinflammatory roles in the pathogenesis of AD.