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Selenium and the Methionine Sulfoxide Reductase System
Derek B. Oien,Jackob Moskovitz
Molecules , 2009, DOI: 10.3390/molecules14072337
Abstract: Selenium is a chemical element participating in the synthesis of selenocysteine residues that play a pivotal role in the enzymatic activity efficiency of selenoproteines. The methionine sulfoxide reductase (Msr) system that reduces methionine sulfoxide (MetO) to methionine comprises the selenoprotein MsrB (MsrB1) and the non-selenoprotein MsrA, which reduce the R- and the S- forms of MetO, respectively. The effects of a selenium deficient (SD) diet, which was administrated to wild type (WT) and MsrA knockout mice (MsrA-/-), on the expression and function of Msr-related proteins are examined and discussed. Additionally, new data about the levels of selenium in brain, liver, and kidneys of WT and MsrA-/- mice are presented and discussed.
Decreased Phosphorylation and Increased Methionine Oxidation of α-Synuclein in the Methionine Sulfoxide Reductase A Knockout Mouse
Derek B. Oien,Gonzalo A. Carrasco,Jackob Moskovitz
Journal of Amino Acids , 2011, DOI: 10.4061/2011/721094
Abstract: Previously, we have showed that overexpression of methionine-oxidized α-synuclein in methionine sulfoxide reductase A (MsrA) null mutant yeast cells inhibits α-synuclein phosphorylation and increases protein fibrillation. The current studies show that ablation of mouse MsrA gene caused enhanced methionine oxidation of α-synuclein while reducing its own phophorylation levels, especially in the hydrophobic cell-extracted fraction. These data provide supportive evidence that a compromised MsrA function in mammalian brain may cause enhanced pathologies associated with altered α-synuclein oxidation and phosphorylation levels. 1. Introduction Parkinson’s disease (PD) is characterized by the formation of neuronal inclusion bodies that are denoted as Lewy bodies [1]. These bodies consist mainly of α-synuclein fibrils [2]. The α-synuclein protein is a presynaptic and its function and involvement in the development of PD is yet to be clearly determined. When α-synuclein is abnormally expressed or modified, various studies indicate it may cause alterations in mitochondrial and proteasomal function, protein aggregation, and accumulation of reactive oxygen species (ROS) [3–6]. Increased ROS and cellular α-synuclein levels promote its aggregation [7, 8] and can cause posttranslational modifications to the methionine (Met) residues of α-synuclein leading to the formation of methionine sulfoxide (MetO)—containing α-synuclein (MetO-α-synuclein). MetO modifications can be present in two forms of enantiomers: Met-S-O and Met-R-O that can be readily reduced by the methionine sulfoxide reductase (Msr) system. Msr type A (MsrA) reduces Met-S-O and Msr type B (MsrB) reduces Met-R-O [9, 10]. MsrA is thought to be the major Msr because it is a positive regulator of MsrB expression levels [11, 12]. Absence of MsrA can cause a hypervulnerability to conditions of oxidative stress [13–17] and shortened lifespan [16, 18]. One possible explanation is that the cellular regulation of aging neurons (e.g., in PD) is altered and consequently causes the accumulation of misfolded proteins (e.g., α-synuclein) [19]. The functional role of phosphorylation to α-synuclein is not completely and clearly understood. Previous work has determined that msrA knockout yeast strain expressing either of the three α-synuclein types (normal type α-synuclein (Syn) and Syn mutant types: SynA30P, SynA53T) showed significantly lower levels of phosphorylation relative to α-synuclein expressed in wild-type cells [22]. These data suggest that increased levels of MetO moiety in α-synuclein could inhibit its
Erratum to “Decreased Phosphorylation and Increased Methionine Oxidation of -Synuclein in the Methionine Sulfoxide Reductase A Knockout Mouse”
Derek B. Oien,Gonzalo A. Carrasco,Jackob Moskovitz
Journal of Amino Acids , 2012, DOI: 10.1155/2012/415713
Erratum to “Decreased Phosphorylation and Increased Methionine Oxidation of -Synuclein in the Methionine Sulfoxide Reductase A Knockout Mouse”
Derek B. Oien,Gonzalo A. Carrasco,Jackob Moskovitz
Journal of Amino Acids , 2012, DOI: 10.1155/2012/415713
Oxidation of Helix-3 Methionines Precedes the Formation of PK Resistant PrPSc
Tamar Canello,Kati Frid,Ronen Gabizon,Silvia Lisa,Assaf Friedler,Jackob Moskovitz,María Gasset,Ruth Gabizon
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1000977
Abstract: While elucidating the peculiar epitope of the α-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the α-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the α-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.
Quantification is Incapable of Directly Enhancing Life Quality through Healthcare  [PDF]
Peter A. Moskovitz
Open Journal of Philosophy (OJPP) , 2013, DOI: 10.4236/ojpp.2013.34A004
Abstract: Quantification, the measurement and representational modeling of objects, events and relationships, cannot enhance life quality, not directly. Illustrative is Sydenham’s model of disease (Sydenham, 1848-1850) and its spawn: the checklist quantification that is contained in the DSM (Diagnostic and Statistical Manual of Mental Disorders, now in its fifth edition) and ICD (International Classification of Diseases, now in its ninth edition). The use of these diagnostic catalogs is incapable of directly enhancing health, a component of life quality; because health is not the control or absence of disease, and practitioners do not think in checklists. Healthcare practitioners have adopted the methods of the airline industry in imposing checklists that are unnatural to nonlinear cognition. At first instance and finally, the subjectivity of experience and the intersubjectivity of communication create the diagnostic and therapeutic relationship that enhances health and life quality. Health is the capacity to cope and to adapt to the experience of suffering, regardless of its cause or context, and to pursue salutary experience. Society will effectively develop, implement and “reform” healthcare only when it accepts positive, noncircular definitions of health and “Quality of Life.” The ethical obligation of the practitioner is to honor and trust the patient’s narrative of illness, the story of suffering.
Variation in MSRA Modifies Risk of Neonatal Intestinal Obstruction in Cystic Fibrosis
Lindsay B. Henderson,Vishal K. Doshi,Scott M. Blackman,Kathleen M. Naughton,Rhonda G. Pace,Jackob Moskovitz,Michael R. Knowles,Peter R. Durie,Mitchell L. Drumm,Garry R. Cutting
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002580
Abstract: Meconium ileus (MI), a life-threatening intestinal obstruction due to meconium with abnormal protein content, occurs in approximately 15 percent of neonates with cystic fibrosis (CF). Analysis of twins with CF demonstrates that MI is a highly heritable trait, indicating that genetic modifiers are largely responsible for this complication. Here, we performed regional family-based association analysis of a locus that had previously been linked to MI and found that SNP haplotypes 5′ to and within the MSRA gene were associated with MI (P = 1.99×10?5 to 1.08×10?6; Bonferroni P = 0.057 to 3.1×10?3). The haplotype with the lowest P value showed association with MI in an independent sample of 1,335 unrelated CF patients (OR = 0.72, 95% CI [0.53–0.98], P = 0.04). Intestinal obstruction at the time of weaning was decreased in CF mice with Msra null alleles compared to those with wild-type Msra resulting in significant improvement in survival (P = 1.2×10?4). Similar levels of goblet cell hyperplasia were observed in the ilea of the Cftr?/? and Cftr?/?Msra?/? mice. Modulation of MSRA, an antioxidant shown to preserve the activity of enzymes, may influence proteolysis in the developing intestine of the CF fetus, thereby altering the incidence of obstruction in the newborn period. Identification of MSRA as a modifier of MI provides new insight into the biologic mechanism of neonatal intestinal obstruction caused by loss of CFTR function.
Colors of Dynamically Associated Asteroid Pairs
Nicholas Moskovitz
Physics , 2012, DOI: 10.1016/j.icarus.2012.07.011
Abstract: Recent dynamical studies have identified pairs of asteroids that reside in nearly identical heliocentric orbits. Possible formation scenarios for these systems include dissociation of binary asteroids, collisional disruption of a single parent body, or spin-up and rotational fission of a rubble-pile. Aside from detailed dynamical analyses and measurement of rotational light curves, little work has been done to investigate the colors or spectra of these unusual objects. A photometric and spectroscopic survey was conducted to determine the reflectance properties of asteroid pairs. New observations were obtained for a total of 34 individual asteroids. Additional photometric measurements were retrieved from the Sloan Digital Sky Survey Moving Object Catalog. Colors or spectra for a total of 42 pair components are presented here. The main findings of this work are: (1) the components in the observed pair systems have the same colors within the uncertainties of this survey, and (2) the color distribution of asteroid pairs appears indistinguishable from that of all Main Belt asteroids. These findings support a scenario of pair formation from a common progenitor and suggest that pair formation is likely a compositionally independent process. In agreement with previous studies, this is most consistent with an origin via binary disruption and/or rotational fission.
Herbal medicinal teas from South Africa
Bhat,RB; Moskovitz,G;
Phyton (Buenos Aires) , 2009,
Abstract: an investigation of herbal medicinal teas from western cape, south africa was conducted to assess the varieties of herbal teas used to treat various ailments. each packet of medicinal tea is a blend of carefully selected four or more herbs which are commonly grown in the organic garden in an ancient valley near the southernmost tip of south africa and some indigenous herbs picked up in the nearby mountains. the teas are specific for the diseased organ/s and also include the herbs to support and strengthen the systems serving the ailing organ/s. the study shows that there are about twenty-one different types of herbal teas, and the packets of 50 g each are sold in south african markets under the trade names of arthritea, asthmitea, constipatea, detoxtea, diabetea, dietea, energetea, flootea, hangovertea, heartburntea, hi lo b p tea, indigestea, kidneytea, liveritea, relaxitea, sleepitea, slimtea, tranquilitea, tummytea, ulcertea, and voomatea. they include 28 herbal species belonging to 12 families. the efficacy of herbal teas and use of traditional remedies are held with high esteem in south africa .
Differentiation of Planetesimals and the Thermal Consequences of Melt Migration
Nicholas Moskovitz,Eric Gaidos
Physics , 2011, DOI: 10.1111/j.1945-5100.2011.01201.x
Abstract: We model the heating of a primordial planetesimal by decay of the short-lived radionuclides Al-26 and Fe-60 to determine (i) the timescale on which melting will occur; (ii) the minimum size of a body that will produce silicate melt and differentiate; (iii) the migration rate of molten material within the interior; and (iv) the thermal consequences of the transport of Al-26 in partial melt. Our models incorporate results from previous studies of planetary differentiation and are constrained by petrologic (i.e. grain size distributions), isotopic (e.g. Pb-Pb and Hf-W ages) and mineralogical properties of differentiated achondrites. We show that formation of a basaltic crust via melt percolation was limited by the formation time of the body, matrix grain size and viscosity of the melt. We show that low viscosity (< 1 Pa-s) silicate melt can buoyantly migrate on a timescale comparable to the mean life of Al-26. The equilibrium partitioning of Al into silicate partial melt and the migration of that melt acts to dampen internal temperatures. However, subsequent heating from the decay of Fe-60 generated melt fractions in excess of 50%, thus completing differentiation for bodies that accreted within 2 Myr of CAI formation (i.e. the onset of isotopic decay). Migration and concentration of Al-26 into a crust results in remelting of that crust for accretion times less than 2 Myr and for bodies >100 km in size. Differentiation would be most likely for planetesimals larger than 20 km in diameter that accreted within ~2.7 Myr of CAI formation.
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