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Vollset Knut Wiik Lennox Robert J. Thorstad Eva B. Auer Samuel Bär Kerstin Larsen Martin H. Mahlum Shad Näslund Joacim Stryhn Henrik Dohoo Ian 《Reviews in Fish Biology and Fisheries》2020,30(4):553-568
Reviews in Fish Biology and Fisheries - A systematic review and meta-analysis was conducted to evaluate the appropriate tag:fish size ratio when tagging juvenile salmonids (genera Oncorhynchus,... 相似文献
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Sarkar G Curran GL Mahlum E Decklever T Wengenack TM Blahnik A Hoesley B Lowe VJ Poduslo JF Jenkins RB 《PloS one》2011,6(12):e28881
Background
Therapeutic intervention of numerous brain-associated disorders currently remains unrealized due to serious limitations imposed by the blood-brain-barrier (BBB). The BBB generally allows transport of small molecules, typically <600 daltons with high octanol/water partition coefficients, but denies passage to most larger molecules. However, some receptors present on the BBB allow passage of cognate proteins to the brain. Utilizing such receptor-ligand systems, several investigators have developed methods for delivering proteins to the brain, a critical requirement of which involves covalent linking of the target protein to a carrier entity. Such covalent modifications involve extensive preparative and post-preparative chemistry that poses daunting limitations in the context of delivery to any organ. Here, we report creation of a 36-amino acid peptide transporter, which can transport a protein to the brain after routine intravenous injection of the transporter-protein mixture. No covalent linkage of the protein with the transporter is necessary.Approach
A peptide transporter comprising sixteen lysine residues and 20 amino acids corresponding to the LDLR-binding domain of apolipoprotein E (ApoE) was synthesized. Transport of beta-galactosidase, IgG, IgM, and antibodies against amyloid plques to the brain upon iv injection of the protein-transporter mixture was evaluated through staining for enzyme activity or micro single photon emission tomography (micro-SPECT) or immunostaining. Effect of the transporter on the integrity of the BBB was also investigated.Principal Findings
The transporter enabled delivery to the mouse brain of functional beta-galactosidase, human IgG and IgM, and two antibodies that labeled brain-associated amyloid beta plaques in a mouse model of Alzheimer''s disease.Significance
The results suggest the transporter is able to transport most or all proteins to the brain without the need for chemically linking the transporter to a protein. Thus, the approach offers an avenue for rapid clinical evaluation of numerous candidate drugs against neurological diseases including cancer. (299 words). 相似文献4.
Interaction between migration behaviour and estuarine mortality in cultivated Atlantic salmon Salmo salar smolts
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K. W. Vollset S. Mahlum J. G. Davidsen H. Skoglund B. T. Barlaup 《Journal of fish biology》2016,89(4):1974-1990
Migration behaviour and estuarine mortality of cultivated Atlantic salmon Salmo salar smolts in a 16 km long estuary were studied using two methods: (1) acoustic telemetry and (2) group tagging in combination with trap nets. Progression rates of surviving individuals through the estuary were relatively slow using both methods [0·38 LT (total length) s?1 v. 0·25 LT s?1]. In 2012, the progression rate was slow from the river to the estuary (0·55 LT s?1) and the first part of the estuary (0·31 LT s?1), but increased thereafter (1·45–2·21 LT s?1). In 2013, the progression rate was fast from the river to the estuary (4·31 LT s?1) but was slower thereafter (0·18–0·91 LT s?1). Survival to the fjord was higher in 2012 (47%) compared to 2013 (6%). Fast moving individuals were more likely to migrate successfully through the estuary compared to slower moving individuals. Adult recapture of coded‐wire‐tagged S. salar was generally low (0·00–0·04%). Mortality hot spots were related to topographically distinct areas such as the river outlet (in 2012) or the sill separating the estuary and the fjord (in 2013). At the sill, an aggregation of cod Gadus morhua predating on cultivated smolts was identified. The results indicate that slow progression rates through the estuary decreases the likelihood of smolts being detected outside the estuary. The highly stochastic and site‐specific mortality patterns observed in this study highlight the complexity in extrapolating mortality patterns of single release groups to the entire smolt run of wild S. salar. 相似文献
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High expression of tumor endothelial marker 7 is associated with metastasis and poor survival of patients with osteogenic sarcoma 总被引:1,自引:0,他引:1
Our objective is to identify genes regulating metastasis of osteogenic sarcoma (OGS) since metastasis is the primary cause of mortality among patients with OGS. To identify such genes, we first created a database of differentially expressed genes between six low-grade and six high-grade OGS tumors, and between a normal immortalized osteoblast cell line (FOB) and four commercially available OGS-derived cell lines. We specifically searched for surface proteins over-expressed in high-grade OGS, since we hypothesize that tumor-cell specific surface markers are key to metastasis. A gene encoding Tumor Endothelial Marker7 (TEM7) was selected as a candidate for further study. TEM7 expression pattern was assessed by RT-PCR, Western blotting and immunostaining. TEM7 mRNA was abundantly expressed in SAOS cells (derived from high-grade OGS), but not in FOB or MG63 cells (derived from low-grade OGS). Virtually no expression of TEM7 protein was observed in FOB cells but abundant expression was noted in SAOS and TE85 cells. Employing immunostaining of 92 human OGS specimens (50 high-grade and 42 low-grade) collected before chemotherapy show 97% (37 of 38) of high-grade OGS specimens with metastasis have high TEM7 staining. Further, we found that elevated expression of TEM7 correlated with poor survival (p<0.04) of affected patients. Inhibiting TEM7 function by siRNA inhibited invasion and migration of OGS cells with metastatic potential. Our results suggest TEM7 expression level closely parallels histology-based prognostication of OGS metastasis and, therefore, it is a therapeutic target. This is the first demonstration of a link between TEM7 and cancer metastasis. 相似文献
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Shad Mahlum David Cote Yolanda F. Wiersma Curtis Pennell Blair Adams 《Restoration Ecology》2018,26(5):952-963
The restoration of 4 partial stream barriers was evaluated in watersheds of Terra Nova National Park, Newfoundland, Canada from 2009 to 2011. Brook trout (n = 462) were tagged and tracked moving through our study sites using passive‐integrated transponder telemetry and the restoration actions were assessed using 3 different measures: passage success rates; the range of passable flows; and the availability of passable flows. We considered the observed results within a before‐after‐control‐impact (BACI) design that included reference reaches and pre‐restoration observations. The conclusions of BACI analyses were also contrasted with those that would have been obtained from commonly used before‐after (B‐A) or control‐impact (C‐I) study designs. While the restoration actions changed hydrological conditions in a way that should facilitate fish passage, our biological measures indicated that success was variable across culverts and within culverts depending on the measure evaluated. Furthermore, the natural temporal and spatial variability of fish movements often resulted in different conclusions between the more robust BACI design and the more commonly used B‐A and C‐I designs. Our results demonstrate that restoration of partial barriers may not always yield dramatic improvements. Furthermore, without suitable controls, the chances of drawing false conclusions regarding restorations in temporally and spatially dynamic systems are substantial. 相似文献
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Michaela B. Benedikt Eric W. Mahlum Kristen L. Shogren Malayannan Subramaniam Thomas C. Spelsberg Michael J. Yaszemski Avudaiappan Maran 《Journal of cellular biochemistry》2010,109(5):950-956
Osteosarcoma is a bone tumor that frequently develops during adolescence. 2‐Methoxyestradiol (2‐ME), a naturally occurring metabolite of 17β‐estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2‐ME actions, we studied the effect of 2‐ME treatment on OPG gene expression in human osteosarcoma cells. 2‐ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2‐ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3‐, 1.9‐, 2.8‐, and 2.5‐fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2‐ME treatment. The effect of 2‐ME on osteosarcoma cells was ligand‐specific as parent estrogen, 17β‐estradiol and a tumorigenic estrogen metabolite, 16α‐hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co‐treating osteosarcoma cells with OPG protein did not further enhance 2‐ME‐mediated anti‐tumor effects. OPG‐released in 2‐ME‐treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2‐ME‐mediated anti‐proliferative effects in osteosarcoma cells, but rather participates in anti‐resorptive functions of 2‐ME in bone tumor environment. J. Cell. Biochem. 109: 950–956, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
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Mandal D Srivastava A Mahlum E Desai D Maran A Yaszemski M Jalal SM Gitelis S Bertoni F Damron T Irwin R O'connor M Schwartz H Bolander ME Sarkar G 《Gene》2007,386(1-2):131-138
Deciphering the molecular basis of cancer is critical for developing novel diagnostic and therapeutic strategies. To better understand the early molecular events involving osteogenic sarcoma (OGS), we have initiated a program to identify potential tumor suppressor genes. Expression profiling of total RNA from ten normal bone cell lines and eleven OGS-derived cell lines by microarray showed 135-fold lower expression of FRZB/sFRP3 mRNA in OGS cells compared to bone cells; this down-regulation of Frzb/sFRP3 mRNA expression was found to be serum-independent. Subsequently, fourteen OGS biopsy specimens showed nine-fold down-regulation of Frzb/sFRP3 mRNA expression compared to expression in eight normal bone specimens as determined by microarray. FRZB /sFRP3 protein level was also found to be at a very low level in 4/4 OGS cell lines examined. Quantitation by RT-PCR indicated approximately 70% and approximately 90% loss of Frzb/sFRP3 mRNA expression in OGS biopsy specimens and OGS-derived cell lines respectively, compared to expression in bone (p<0.0001). Hybridization experiments of a cDNA microarray containing paired normal and tumor specimens from nineteen different organs did not show any significant difference in the level of Frzb/sFRP3 mRNA expression between the normal and the corresponding tumor tissues. Exogenous expression of FRZB/sFRP3 mRNA in two OGS-derived cell lines lacking endogenous expression of the mRNA produced abundant mRNA from the exogenous gene, eliminating degradation as a possibility for very low level of FRZB/sFRP3 mRNA in OGS specimens. Results from PCR-based experiments suggest that the FRZB/sFRP3 gene is not deleted in OGS cell lines, however, karyotyping shows gross abnormalities involving chromosome 2 (location of the FRZB gene) in five of twelve OGS-derived cell lines. Together, these data suggest a tumor-suppressive potential for FRZB/sFRP3 in OGS. 相似文献
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Mahlum E Mandal D Halder C Maran A Yaszemski MJ Jenkins RB Bolander ME Sarkar G 《Analytical biochemistry》2007,365(2):215-221
Noncovalent protein delivery into cells via peptide carriers is an emerging concept. Only a handful of such peptides are known. To address various limitations associated with protein delivery for therapeutic purposes, a greater number of different delivery peptides would be required. No general method exists for creating such peptides. By combining a sequence of 16 lysine residues (K16) with the signal peptide (SP) sequence of Kaposi's fibroblast growth factor (K-FGF), we have synthesized a peptide (K16SP) that efficiently and noncovalently delivers functionally intact proteins (immunoglobulin G molecules, beta-galactosidase, and green fluorescent protein) into mammalian cells. The peptides K16 and SP each alone did not show any noncovalent protein-carrying capacity. K16SP appears to be nontoxic to cells and three to four times more efficient than a commercially available peptide reagent. Our approach offers proof-of-concept of a general strategy for creating a diverse array of peptide carriers for eventual therapeutic applications. 相似文献