Safa Rose - Academia.edu (original) (raw)

Papers by Safa Rose

Cytotechnology, 1994

Fatty acids (FAs) have long been recognized for their nutritional value in the absence of glucose... more Fatty acids (FAs) have long been recognized for their nutritional value in the absence of glucose, and as necessary components of cell membranes. However, FAs have other effects on cells that may be less familiar. Polyunsaturated FAs of dietary origin (n−6 andn−3) cannot be synthesized by mammals, and are termed ‘essential’ because they are required for the optimal biologic function of specialized cells and tissues. However, they do not appear to be necessary for normal growth and metabolism of a variety of cells in culture. The essential fatty acids (EFAs) have received increased attention in recent years due to their presumed involvement in cardiovascular disorders and in cancers of the breast, pancreas, colon and prostate. Manyin vitro systems have emerged which either examine the role of EFAs in human disease directly, or utilize EFAs to mimic thein vivo cellular environment. The effects of EFAs on cells are both direct and indirect. As components of membrane phospholipids, and due to their varying structural and physical properties, EFAs can alter membrane fluidity, at least in the local environment, and affect any process that is mediated via the membrane. EFAs containing 20 carbons and at least three double bonds can be enzymatically converted to eicosanoid hormones, which play important roles in a variety of physiological and pathological processes. Alternatively, EFAs released into cells from phospholipids can act as second messengers that activate protein kinase C. Furthermore, susceptibility to oxidative damage increases with the degree of unsaturation, a complication that merits consideration because lipid peroxidation can lead to a variety of substances with toxic and mutagenic properties. The effects of EFAs on cultured cells are illustrated using the responses of normal and tumor human mammary epithelial cells. A thorough evaluation of EFA effects on commercially important cells could be used to advantage in the biotechnology industry by identifying EFA supplements that lead to improved cell growth and/or productivity.

Fish Physiology and Biochemistry

In this study, we examine changes in fatty acid composition of polar and neutral lipids in gill, ... more In this study, we examine changes in fatty acid composition of polar and neutral lipids in gill, liver, and muscle of freshwater alewives (Alosa pseudoharengus) after temperature challenges in the laboratory. Alewives experienced either a warm or cold challenge in which temperatures were raised or lowered 0.5°C day−1 over 4–6 weeks. In alewives experiencing the cold challenge, gill polar lipids showed evidence of significant remodeling, including decreases in palmitic acid and saturated fatty acids and increases in n-3 and n-6 highly unsaturated fatty acids including docosahexaenoic acid (DHA) and arachidonic acid. In alewives experiencing the warm challenge, we observed significant increases in saturated fatty acids (due mainly to increased palmitic acid) and decreases in polyunsaturated fatty acids in polar lipids of muscle and liver tissue. Fish that died during the cold challenge had significantly higher levels of palmitic acid in muscle polar lipids compared to fish that survived; fish that died during the warm challenge displayed complex changes in fatty acid composition. Based on theoretical considerations, the changes in polar lipids we observed during thermal acclimation are likely to promote appropriate membrane fluidity under each thermal regime. The increased incorporation of highly unsaturated fatty acids during cold acclimation could have significant physiological and ecological implications. In particular, since highly unsaturated fatty acids are typically scarce in freshwater food webs, dietary deficiencies in these essential fatty acids may be a significant factor in winter mortality of freshwater alewives.

Marine Biology, 2003

The impact of supplementing lipid emulsions rich in eicosapentaenoic acid (EmEPA), docosahexaenoi... more The impact of supplementing lipid emulsions rich in eicosapentaenoic acid (EmEPA), docosahexaenoic acid (EmDHA) or saturated fatty acids (EmCOCO) to a standard algal diet [3:1 mixture of Isochrysis galbana (T-iso) and Chaetoceros neogracile, St-diet] on Argopecten purpuratus broodstock was evaluated. Broodstock fecundity was compared as well as the egg quality in terms of lipid content, fatty acid composition and lipid class distribution. Fecundity was defined as the number of eggs released in the spawning process, since spawning was virtually complete. Results indicated that the total lipid content of the eggs of A. purpuratus was diet independent. A greater energy reserve was spent on a larger number of oocytes and not on bigger sized oocytes with a higher lipid content. The lipids supplied through the emulsions were at least partially allocated to the eggs, demonstrating that the fatty acid composition of the eggs could be manipulated, especially the neutral lipid fraction. Levels of EPA changed more rapidly than DHA levels, supporting the observation that they fulfilled an energetic and structural role, respectively. The St-diet supplemented with 50%EmCOCO resulted in a significantly higher fecundity compared to the algal diet supplemented with 25%EmEPA+25%EmDHA and the non-supplemented algal diet. It would seem that saturated fatty acids (SAFA) were more easily or preferentially incorporated in the female gonads of A. purpuratus. The relative content of SAFA and 18:2(n-6) in these eggs rose significantly. The relative content of the highly unsaturated fatty acids, EPA and DHA, on the other hand was substantially lower in the neutral lipid fraction, but hardly affected in the polar lipid fraction. It appeared that the maintenance of an adequate DHA/EPA ratio (approximately 1.2) was more important than the absolute levels of the two fatty acids, as long as a threshold value was reached.

Among bacteria, the chaperone-usher (CU) pathway is a widespread conserved assembly and transloca... more Among bacteria, the chaperone-usher (CU) pathway is a widespread conserved assembly and translocation system for adhesive protein fibres, called pili or fimbriae. Pili are large linear polymers that protrude from the outer bacterial surface and consist of several subunits. Pili contain adhesin proteins at the tip that are used by pathogenic bacteria to mediate attachment to host cells and initiate infections. Well studied examples of CU pili are P and type 1 pili of uropathogenic Escherichia coli (UPEC), which are responsible for kidney and bladder infections, respectively. Upon secretion into the periplasm, pilus subunits are stabilized by periplasmic chaperones and the resulting chaperone:subunit complexes are guided to the usher located in the outer membrane. The usher catalyzes the ordered assembly of pilus subunits while releasing the chaperones and translocating the growing pilus stepwise to the outer surface. Here we review the structural biology of the chaperone-usher pathway that has helped to understand the mechanisms by which biogenesis of an important class of bacterial organelles occurs.

American Journal of Clinical Oncology-cancer Clinical Trials, 2006

To evaluate the feasibility and efficacy of sequential neoadjuvant chemotherapy, chemoradiation, ... more To evaluate the feasibility and efficacy of sequential neoadjuvant chemotherapy, chemoradiation, and surgery in patients with locally advanced esophageal cancer. There were 29 patients who received paclitaxel 150 mg/m2 and gemcitabine 3000 mg/m2 2 weeks apart. Two weeks later, patients received cisplatin 75 mg/m2 and 5-fluorouracil (5-FU) 1000 mg/m2/d continuous infusion for 4 days with concurrent radiotherapy in 15 fractions to a total dose of 4000 cGy. After 6 weeks, cisplatin and 5-FU were repeated at the above doses. After 4 to 6 weeks, patients were restaged and underwent surgical resection. All 29 patients completed the prescribed gemcitabine, paclitaxel, and radiation therapy. Febrile neutropenia occurred in 1 patient and 4 patients received growth factor support. After neoadjuvant treatment, 1 patient refused surgery, 23 underwent R0 resection (82%), while 5 developed progressive disease. Four patients developed anastomotic leaks (17%). Four patients had complete pathologic responses (14%) and 4 (14%) had only residual microscopic disease. Nine patients remain alive at a median follow-up of 48 months. Three-year survival for the entire cohort was 36%. This regimen was associated with a high rate of compliance and induction therapy had an acceptable toxicity profile. The R0 resection rate and 3-year survival data are similar to recently reported studies. While active, gemcitabine and paclitaxel induction therapy was associated with an increased rate of postoperative complications, but no increase in survival. Patterns of failure continue to demonstrate the need for regimens incorporating greater emphasis on systemic therapy for locally advanced esophageal cancer.

Molecular Cell, 2006

Gram-negative pathogens commonly use the chaperone-usher pathway to assemble adhesive multisubuni... more Gram-negative pathogens commonly use the chaperone-usher pathway to assemble adhesive multisubunit fibers on their surface. In the periplasm, subunits are stabilized by a chaperone that donates a b strand to complement the subunits' truncated immunoglobulin-like fold. Pilus assembly proceeds through a ''donor-strand exchange'' (DSE) mechanism whereby this complementary b strand is replaced by the N-terminal extension (Nte) of an incoming pilus subunit. Using X-ray crystallography and real-time electrospray ionization mass spectrometry (ESI-MS), we demonstrate that DSE requires the formation of a transient ternary complex between the chaperone-subunit complex and the Nte of the next subunit to be assembled. The process is crucially dependent on an initiation site (the P5 pocket) needed to recruit the incoming Nte. The data also suggest a capping reaction displacing DSE toward product formation. These results support a zip-in-zip-out mechanism for DSE and a catalytic role for the usher, the molecular platform at which pili are assembled.

Neuromuscular Disorders, 2010

The skeletal muscle ryanodine receptor plays a crucial role in excitation-contraction (EC) coupli... more The skeletal muscle ryanodine receptor plays a crucial role in excitation-contraction (EC) coupling and is implicated in various congenital myopathies. The periodic paralyses are a heterogeneous, dominantly inherited group of conditions mainly associated with mutations in the SCN4A and the CACNA1S genes. The interaction between RyR1 and DHPR proteins underlies depolarization-induced Ca 2+ release during EC coupling in skeletal muscle. We report a 35-yearold woman presenting with signs and symptoms of a congenital myopathy at birth and repeated episodes of generalized, atypical normokalaemic paralysis in her late teens. Genetic studies of this patient revealed three heterozygous RYR1 substitutions (p.Arg2241X, p.Asp708Asn and p.Arg2939Lys) associated with marked reduction of the RyR1 protein and abnormal DHPR distribution. We conclude that RYR1 mutations may give rise to both myopathies and atypical periodic paralysis, and RYR1 mutations may underlie other unresolved cases of periodic paralysis with unusual features.

Annals of The Association of American Geographers, 2004

This article examines survival strategies of urban households in post-socialist cities during the... more This article examines survival strategies of urban households in post-socialist cities during the transition from the Soviet system to a market economy. The article links the outcomes of systemic transformation to the daily lives of households and connects urban change induced by mass privatization to class and gender processes inside the households. These ''other transitions'' in everyday class and gender processes are consistently overlooked by macroeconomic approaches that dominate among transition theorists and policy consultants. The focus is on households in a Moscow neighborhood who attempt to meet the competing demands of earning income, fulfilling domestic responsibilities, and securing child care in a rapidly changing urban context. The diverse formal and informal economic practices of households are analyzed using the model of ''multiple economies'' that include paid work, informal work for cash, unpaid domestic labor, and help in kind, labor, and cash from networks of extended family, friends, and neighbors. Mapping the typically invisible transformations of multiple economies of households contributes to creating alternative geographies of transition that are rooted in daily household experiences, acknowledges the existence of multiple economies practices, and emphasizes their importance for household social reproduction.

European Journal of Nuclear Medicine, 1985

The results of sodium iodide 131I treatment of thyrotoxicosis in 1,168 patients (302 males, 866 f... more The results of sodium iodide 131I treatment of thyrotoxicosis in 1,168 patients (302 males, 866 females; 58.5% diffuse and 41.5% multinodular toxic goitre) are presented. At the end of the 1st year post-treatment, 54.4% were hypothyroid, and the incidence of hypothyroidism after the 2nd year increased by 3% per year. When the results were analysed according to the calculated radiation dose the thyroid, it was found that the cumulative incidence of hypothyroidism from 6 months to 2 years posttreatment rose almost proportionally to the dose in cases of doses of 1,500–15,000 rad, but increased very little for higher doses; however, the long-term incidence of hypothyroidism was almost independent of the thyroid dose. Multivariate analysis showed that the results of 131I therapy at 6 months depended also on sex (treatment being more effective in women), the consistency of the thyroid gland and the year of treatment, with the same radiation dose giving a higher incidence of hypothyroidism in patients treated recently, in comparison to those treated early in the period studied. Of the patients treated in the period 1978–1982 (mean dose, 300 μCi/g), 93.5% were cured with a single dose of 131I, and 78% were hypothyroid at 6 months post-treatment.

Journal of Neurology Neurosurgery and Psychiatry, 2007

The case is reported of a patient with progressive proximal and distal weakness, dysphagia, respi... more The case is reported of a patient with progressive proximal and distal weakness, dysphagia, respiratory weakness, calcifications, ptosis and ophthalmoparesis with inflammation, rimmed vacuoles and positive amyloid and ubiquitin on muscle biopsy. The histopathological features fit best with inclusion body myositis, but ophthalmoparesis and ptosis have not previously been described. The clinical phenotype fits best with hereditary inclusion body myopathy or distal-oculopharyngeal muscular dystrophy, but the degree of inflammation seen is unusual. None of these are associated with calcinosis.