Study of mechanisms involved in the collision-induced dissociation of carboxylate anions from glycerophospholipids using negative ion electrospray tandem quadrupole mass spectrometry

The collision-induced dissociation of the carboxylate anions from human blood phosphatdilycholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidic acid (PA) containing the C18:0 (sn-1) and C20:4 (sn-2) fatty acyl residues was studied using normal phase liquid chromatography coupled with negative ion electrospray tandem mass spectrometry. The product ion peak area ratio of C18:0 to C20:4 was calculated for each phospholipid species and was found to increase with increasing collision energy for all classes. For the phospholipids with a net neutral charge (PE, PC) there was a preferential loss of the sn-2 carboxylate anion (C20:4) at low collision energy, while at higher energy there was a preferential loss of the sn-1 carboxylate anion (C18:0). For the phospholipids with a net negative charge (PI, PA, PS) the intensity of the sn-1 carboxylate anion peak was equal to or higher than the sn-2 carboxylate anion peak at the energies measured. At a given collision energy the product ion peak area ratio decreased in the order PA > or = PS > PI. Studying PS and PE species at different collision energies, it was found that for both classes the increase in the abundance ratio with increasing collision energy was largely dependent on the chain length and degree of unsaturation of the sn-2 acyl chain.     

Charge movement by the Na/K pump in Xenopus oocytes

Pre-steady-state transient currents (1986. Nakao, M., and D. C. Gadsby. Nature [Lond.]. 323:628-630) mediated by the Na/K pump were measured under conditions for Na/Na exchange (K-free solution) in voltage-clamped Xenopus oocytes. Signal-averaged (eight times) current records obtained in response to voltage clamp steps over the range -160 to +60 mV after the addition of 100 microM dihydroouabain (DHO) or removal of external Na (control) were subtracted from test records obtained before the solution change. A slow component of DHO- or Na-sensitive difference current was consistently observed and its properties were analyzed. The quantity of charge moved was well described as a Boltzmann function of membrane potential with an apparent valence of 1.0. The relaxation rate of the current was fit by the sum of an exponentially voltage-dependent reverse rate coefficient plus a voltage-independent forward rate constant. The quantity of charge moved at the on and off of each voltage pulse was approximately equal except at extreme negative values of membrane potential where the on charge tended to be less than the off. The midpoint voltage of the charge distribution function (Vq) was shifted by -24.8 +/- 1.7 mV by changing the external [Na] in the test condition from 90 to 45 mM and by +14.7 +/- 1.7 mV by changing the test [Na] from 90 to 120 mM. A pseudo three-state model of charge translocation is discussed in which Na+ is bound and occluded at the internal face of the enzyme and is released into an external-facing high field access channel (ion well). The model predicts a shift of the charge distribution function to more hyperpolarized potentials as extracellular [Na] is lowered; however, several features of the data are not predicted by the model.     

Fast inactivation in Shaker K+ channels. Properties of ionic and gating currents

Fast inactivating Shaker H4 potassium channels and nonconducting pore mutant Shaker H4 W434F channels have been used to correlate the installation and recovery of the fast inactivation of ionic current with changes in the kinetics of gating current known as "charge immobilization" (Armstrong, C.M., and F. Bezanilla. 1977. J. Gen. Physiol. 70:567-590.). Shaker H4 W434F gating currents are very similar to those of the conducting clone recorded in potassium-free solutions. This mutant channel allows the recording of the total gating charge return, even when returning from potentials that would largely inactivate conducting channels. As the depolarizing potential increased, the OFF gating currents decay phase at -90 mV return potential changed from a single fast component to at least two components, the slower requiring approximately 200 ms for a full charge return. The charge immobilization onset and the ionic current decay have an identical time course. The recoveries of gating current (Shaker H4 W434F) and ionic current (Shaker H4) in 2 mM external potassium have at least two components. Both recoveries are similar at -120 and -90 mV. In contrast, at higher potentials (-70 and -50 mV), the gating charge recovers significantly more slowly than the ionic current. A model with a single inactivated state cannot account for all our data, which strongly support the existence of "parallel" inactivated states. In this model, a fraction of the charge can be recovered upon repolarization while the channel pore is occupied by the NH2-terminus region.     

Convenient colorimetric and fluorometric assays for S-nitrosothiols

S-nitrosothiols have been shown to affect a number of physiological functions. Several techniques have been used to detect these species in biological systems, primarily by methods utilizing chemiluminescence. Since the apparatus required for measurement of chemiluminescence are not readily available in most laboratories, methods employing more conventional techniques such as uv-vis and fluorescence spectroscopy may be of greater use. Herein, we report the development of colorimetric and fluorometric methods for the reliable quantitation of S-nitrosothiols. Solutions containing sulfanilamide/N-(1-naphthyl)- ethylenediamine dihydrochloride or 2,2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid), when exposed to S-nitrosoglutathione (GSNO), S-nitrosocysteine, or S-nitrosoacteylpenicillamine, resulted in no absorbance changes in the range of 400-800 nm. Exposure to HgCl2 or Cu(acetate)2 resulted in release of nitric oxide (NO) from the S-nitrosothiols. The liberated NO reacted subsequently with oxygen and formed a chemical species which reacted with either analysis solution, resulting in an increase in absorption between 400 and 800 nm. A plot of RSNO versus absorbance was linear for both mercury(II) and copper(II) ions where the slope in the presence of mercury ion was significantly greater than that for copper ion. The sensitivity was as low as 5 microM RSNO using HgCl2. The fluorometric method using 2, 3-diaminonaphthalene as the scavenger of the NOsolidusO2 products gave a sensitivity of 50 nM for GSNO. In addition, S-nitrosylated proteins were quantitated using the fluorometric technique. These methods provide accurate determination of low concentrations of S-nitrosothiols, utilizing conventional spectroscopic techniques available in most laboratories.     

Exploring infrared wavelength matrix-assisted laser desorption/ionization of proteins with delayed-extraction time-of-flight mass spectrometry

We report a study of the application of delayed extraction (DE) to infrared-wavelength matrix-assisted time-of-flight mass spectrometry (IR-MALDI-TOF-MS) of proteins. The shapes of the spectral peaks obtained with DE-IR-MALDI-MS are compared with those obtained from the same samples and matrix using continuous extraction (CE) IR-MALDI-MS. Application of DE results in significant improvements in the peak resolution, revealing spectral features (in proteins with molecular masses < 12 kDa) that were not resolved in the corresponding CE-IR-Maldi mass spectra. Particularly significant is a series of peaks on the high mass side of the protonated protein peaks that arise through replacement of protons by adventitious sodium ions in the sample. We deduced that these sodium replacement species are a significant contributor to the broad tails (and resulting peak asymmetries) that are a feature of the DE-IR-MALDI mass spectra of proteins with molecular masses > or = 17 kDa. The peak width reduction observed in IR-MALDI by DE suggests that, as in UV-MALDI, the initial velocity distribution for ions produced in the MALDI process contributes to the peak broadness in the CE mass spectra. In a systematic comparison between DE UV-MALDI and DE IR-MALDI, we determined that photochemical matrix adduction is present in UV-MALDI but absent in IR-MALDI. In addition, we find that protein ions produced by IR irradiation are less internally excited (i.e., cooler), exhibiting less fragmentation, more Na+ replacement and/or unspecified noncovalent adduction, and more heme adduction with apomyoglobin. Thus, IR-MALDI appears to be a softer means for producing gas-phase protein ions than is UV-MALDI. It will be of considerable practical interest to determine whether large protein ions produced by IR-MALDI are sufficiently cool to survive transport through reflecting TOF mass spectrometers (without loss of small neutral species such as H2O, NH3, and CO2) and the extended time periods required for detection by quadrupole ion trap and Fourier transform ion cyclotron resonance mass analyzers.     

Experimental charge density distribution and its correlation to structural and optical properties of Sm~(3+) doped Nd_2O_3 nanophosphors

Pure and Sm~(3+) doped Nd_2 O_3 nanophosphors were synthesized using modified Pechini method. The phase formation with symmetry of the sample is confirmed by the Rietveld refinement of the powder Xray diffraction(PXRD) data. The surface morphology and the crystallite size were examined using scanning electron microscopy(SEM) and transmission electron microscopy(TEM) and the results confirmed that the synthesized particles are in nanosize. The energy-dispersive X-ray(EDX) analysis was done to confirm the purity of the sample. The optical properties of the sample were studied using ultraviolet-visible range(UV-Vis) spectroscopic analysis and photoluminescence studies. The calculated band gap of the synthesized Nd_2 O_3 was found to be higher than that of bulk Nd_2 O_3. The photoluminescence(PL) of the prepared samples reveals that doping with Sm3+ ion has influenced the optical properties. Quantitative investigation on charge density distribution was done by analysing the 3-dimensional and 2-dimensional charge density maps drawn along the bonding directions. The maximum entropy method(MEM)/Rietveld analysis was used for the first time to analyse the charge density in the chosen system. Charge density arrangement in the unit cell is correlated to the analysed photoluminescent(PL) properties. The spectral behaviour of the samples has been explained through charge ordering which are verified using experimental data obtained. The studies on these materials have shown that these nanophosphors will provide promising application for near-ultraviolet lightemitting diodes(n-UV-LEDs).     

pH电位滴定法测定黄芩苷钴(II)配合物的稳定常数

为研究植物对土壤重金属污染进行修复时形成的配合物的稳定性,实验以黄芩苷-钴(II)配合物为例进行探讨。在常温常压下,采用pH电位滴定的方法,对黄芩苷与钴离子生成配合物的稳定常数进行了测定。通过使用氢氧化钾标准溶液对一定溶液体系中的黄芩苷溶液及其与钴离子的混合溶液分别进行滴定,借助自动电位数据采集软件记录其反应过程中溶液pH值变化,用生成函数截距法计算出了黄芩苷-Co(II)配合物的一级和二级稳定常数分别为lgK_CoA1=5.89,lgK_CoA2=5.07。通过对黄芩苷-Co(II)配合物各物种在不同pH值条件下的分布进行分析可知,在pH＞8的环境下,有利于配合物的合成,可为被重金属污染的弱碱性土壤进行修复时采用植物修复技术提供理论依据。     

Injury probability and risk in frontal crashes: effects of sorting techniques on priorities for offset testing

A hydrazinonicotinamide-functionalized cyclic platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist [HYNICtide, cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-(6-hydrazinonicotina mido)hexanamide)))] was labeled with 99mTc using tricine and a series of imine-N-containing heterocycles as coligands. The imine-N-containing heterocycles include N-omega-Acetylhistamine (HIS-AC), N-(2-hydroxyethyl)isonicotinamide (ISONIC-HE), isonicotinic acid (ISONIC), isonicotinoyl-L-aspartic acid dimethyl ester (ISONIC-L-Asp-OMe2), 4-methyl-5-thiazoleethanol (MTE), nicotinic acid (NIC), 3-nitro-1,2,4-triazole (NTZ), 4-pyridylacetic acid (PA), 4-pyridineethanesulfonic acid (PES), and 3-pyridinesulfonic acid (PSA). The synthesis of these new ternary ligand [99mTc]HYNICtide complexes can be performed in one or two steps in high yield and high specific activity (>/=10 000 Ci/mmol HYNICtide). For example, the reaction of HYNICtide, [99mTc]pertechnetate, nicotinic acid, stannous chloride, and tricine at pH approximately 5 and 100 degreesC for 20 min results in the complex [99mTc(HYNICtide)(tricine)(NIC)] in >/=90% yield as determined by radio-HPLC. It was found that ternary ligand technetium complexes, [99mTc(HYNICtide)(tricine)(L)] (L = ISONIC, ISONIC-L-Asp-OMe2, ISONIC-HE, MTE, PA, PES, and PSA) are formed as equal mixtures of two isomeric forms. Complex [99mTc(HYNICtide)(tricine)(L)] (L = HIS-AC and NTZ) showed more than two well-resolved radiometric peaks at the retention times of interest, suggesting that they may have more than two forms in solution due to different bonding modalities of HIS-AC and NTZ. By a chirality experiment, it was found that the presence of two radiometric peaks is a result of the resolution of the two diastereomers which are formed by the combination of the chiral HYNICtide and the chiral technetium chelate. The formation of two diastereomers was also observed when a chiral imine-N-containing coligand was used for the radiolabeling of HYNIC-BA. The new ternary ligand [99mTc]HYNICtide complexes were found to be stable for up to 6 h in the reaction mixture. The high solution stability is attributed to their kinetic inertness. The composition of these complexes was determined to be 1:1:1:1 for Tc:HYNICtide:L:tricine (L = imine-N-containing heterocycles) through a series of mixed ligand experiments on the tracer (99mTc) level. The lipophilicity of the ternary ligand [99mTc]HYNICtide complexes can be systematically varied by the choice of polyaminocarboxylate and imine-N-containing coligands. Using the combination of tricine and an imine-N-containing coligand, HYNIC-derivatized peptides or other small molecules can be labeled with 99mTc in high specific activity and high stability for potential use as radiopharmaceuticals.     

beta-Fructosidases: a new superfamily of glycosyl-hydrolases

Dihydropyridines (DHPs) block L-type Ca2+ channels more potently at depolarized membrane potentials, consistent with high affinity binding to the inactivated state. Nisoldipine (a DHP antagonist) blocks the smooth muscle channel more potently than the cardiac one, a phenomenon observed not only in native channels but also in expressed channels. We examined whether this tissue specificity was attributable to differences of inactivation in the two channel types. We expressed cardiac or smooth muscle alpha1C subunits in combination with beta2a and alpha2/delta subunits in human embryonic kidney cells, and used 2 mM Ca2+ as the permeant ion. This system thus reproduces the in vivo topology and charge carrier of the channels while facilitating comparison of the two alpha1C splice variants. Both voltage-dependent and isoform-specific sensitivity of 10 nM nisoldipine inhibition of the channel were demonstrated, with the use of -100 mV as the holding potential for fully reprimed channels and -65 mV to populate the inactivated state. Under drug-free conditions, we characterized fast inactivation (1-sec prepulses) and slow inactivation (3 min prepulses) in the two isoforms. Inactivation parameters were not statistically different in the two channel isoforms; if anything, cardiac channels tended to inactivate more than the smooth muscle channels at relevant voltages. Likewise, the voltage-dependent activation was identical in the two isoforms. We thus conclude that the more potent nisoldipine inhibition of smooth muscle versus cardiac L-type Ca2+ channels is not attributable to differences in channel inactivation or activation. Intrinsic, gating-independent DHP receptor binding affinity differences must be invoked to explain the isoform-specific sensitivity of the DHP block.     

Butanedione monoxime promotes voltage-dependent inactivation of L-type calcium channels in heart. Effects on gating currents

The effect of 20 mM extracellularly applied 2,3-Butanedione monoxime (BDM) on L-type Ca2+ channel charge movement current was studied in whole-cell voltage-clamped guinea-pig ventricular myocytes. Intramembraneous charge movement in response to depolarizing pulses (charge 1), was reduced after the application of BDM. The effect was more pronounced at the OFF of the charge transient (41%) than at the ON (7%). The steady-state availability curve of charge 1 was shifted to the left; the magnitude of the voltage shift was similar to the shift in Ca2+ current availability. Charge movement recorded in the negative voltage range (charge 2) after conditioning depolarizing pulses of different duration, was increased by BDM. For a 300-ms conditioning pulse charge 2 measured during a negative test pulse increased 40% (in Ba2+ external solution) or 35% (in Ca2+ external solution). These results show that BDM promotes voltage-dependent inactivation of L-type Ca2+ channels in parallel with charge interconversion between intramembranous charges 1 and 2. Mechanistically they are consistent either with dephosphorylation or a dihydropyridine-like action, but argue against open channel block as the mechanism of the effect of the drug.     

Inorganic Speciation of Rare Earth Elements in Chaohu Lake and Longganhu Lake, East China

Geochemical behaviors of the rare earth elements(REEs)in river and lake water bodies are dependentmainly on water chemistry and other factors,andhence their variationsin concentration and compositionreflect changes of various environmental variables.There…     

Synthesis, Structure and Ionic Conductivity of La2／3-x Li3x MoO4

AlargenumberofM0 .5A0 .5M′O4 (M :rareearthion ,Bi3+,Fe3+,Cr3+,etc .A :alkaliion ,Cu+,Ag+,etc .M′ :Mo ,W )withtetragonalscheelite typestructurehavegoodcatalyticproperties .Aslumines centsubstrates ,theyhaveexcellentsensitizationtolu minescenceofrareearthion .Manyresearchesontheirstructure ,catalytic ,magneticandluminescentproper tieshavebeenmadesince 196 0s[1～ 10 ] .Thegeneralformulaforcompoundswiththetetragonalscheelite typestructureisAM′O4 wherethecationM′istetrahe drallycoordinat…     

The nature of the excited state of the reaction center of photosystem II of green plants: a high-resolution fluorescence spectroscopy study

We studied the electronically excited state of the isolated reaction center of photosystem II with high-resolution fluorescence spectroscopy at 5 K and compared the obtained spectral features with those obtained earlier for the primary electron donor. The results show that there is a striking resemblance between the emitting and charge-separating states in the photosystem II reaction center, such as a very similar shape of the phonon wing with characteristic features at 19 and 80 cm-1, almost identical frequencies of a number of vibrational modes, a very similar double-Gaussian shape of the inhomogeneous distribution function, and relatively strong electron-phonon coupling for both states. We suggest that the emission at 5 K originates either from an exciton state delocalized over the inactive branch of the photosystem or from a fraction of the primary electron donor that is long-lived at 5 K. The latter possibility can be explained by a distribution of the free energy difference of the primary charge separation reaction around zero. Both possibilities are in line with the idea that the state that drives primary charge separation in the reaction center of photosystem II is a collective state, with contributions from all chlorophyll molecules in the central part of the complex.     

Topographic comparison of the expression of norepinephrine transporter, tyrosine hydroxylase and neuropeptide Y mRNA in association with dopamine beta-hydroxylase neurons in the rabbit brainstem

In mammalian species, ovulation occurs following a massive release of hypothalamic gonadotropin-releasing hormone (GnRH). Several chemicals, including norepinephrine (NE) and neuropeptide Y (NPY), are responsible for the initiation and/or magnitude and duration of this pre-ovulatory GnRH surge. In the central nervous system, NE neural cell bodies are located in the brainstem; some are co-localized with NPY neurons and/or co-express the NE transporter (NET) gene which dictates NET protein production. The activity of NET at NE terminals is critical for synaptic NE function. In the rabbit, coitus induces a hypothalamic NE release which precedes the GnRH surge. We hypothesize that the coital stimulus is transmitted to the brainstem and transformed and integrated into GnRH-stimulating signals via NE, NET and/or NPY. However, very little is known about the distribution of cells expressing NET, NPY and tyrosine hydroxylase (TH, the rate-limiting enzyme of NE synthesis) in this species. Therefore, we utilized the sensitive in situ hybridization technique to identify the presence of these messages in conjunction with the location of NE cells, the latter being marked by dopamine beta-hydroxylase (DBH), the specific enzyme for NE synthesis. Three non-mated New Zealand White does were perfused with 4% paraformaldehyde and their brainstems were sectioned at 20-micron thick between 2 mm caudal to the obex and the rostral pons. Serial sections were immunohistochemically stained for DBH and hybridized with rabbit-specific TH and NET cRNAs and a human NPY probe. The data suggest that several DBH-positive areas in the medulla expressed one or more messages, i.e. the lateral tegmentum (A1) and the nucleus of the solitary tract (A2) expressed all three mRNAs, the area postrema (AP) contained NET and TH mRNAs but not NPY cells. In the pons, the locus coeruleus (LC), subnucleus of coeruleus (LCs) and lateral tegmental nuclei (A5) expressed NET and TH mRNAs but contained little or no NPY message. The distribution patterns of TH and NET appeared to be similar in the LC, LCs, A2 and AP.     

Comparative study of monoclonal antibody scan in diagnosing orthopaedic infection

When clinical data are insufficient to diagnose infection of bone or joints, nuclear scanning becomes crucial in making an accurate diagnosis. The efficacy of (99m)technetium antigranulocyte monoclonal antibody Fab' fragment (LeukoScan) is prospectively compared with (111)indium white blood cell and (99m)technetium methylene diphosphonate bone scans in 74 patients with suspected musculoskeletal infections. They were grouped according to site of suspected infection: 33 long bones, 23 prosthetic joints, and 18 diabetic feet. Sixty-two of these 74 patients had surgical verification with histopathology or culture. The remaining 12 patients had clinical followup as proof of absence of infection. The overall sensitivity of LeukoScan, (111)indium white blood cell, and (99m)technetium methylene diphosphonate bone scans was 93%, 85% and 92%, respectively. Specificity was 89%, 75% and 52%, and accuracy was 90%, 79% and 74%, respectively. The conclusion from this study is that LeukoScan is more accurate in detecting osteomyelitis, with better sensitivity and specificity in prosthetic joints. Compared with (111)indium white blood cell scans, LeukoScan++ gives superior images, and results are obtained in 1 to 6 hours without biohazard risk from handling blood products.     

Diffusion Coefficient of Calcium Ion in CaO-Al_2O_3-SiO_2 Melts

 The Nernst-Einstein equation is used to calculate the diffusion coefficient of calcium ion in the CaO-Al2O3-SiO2 system based on the data of the density and electrical conductivity. It is assumed that all the aluminium ions form tetrahedral structure and merge with chain or ring in the case of molar concentration of CaO higher than Al2O3. And in this case, calcium ion is assumed to be the conclusive charge carrier. A formula between the diffusion coefficient and concentration of calcium ion as well as temperature is deduced, which gives an increasing function relation between the diffusion coefficient and the concentration of calcium ions.     

Molecular weight determination of megadalton DNA electrospray ions using charge detection time-of-flight mass spectrometry

We present results obtained with a novel mass spectrometer capable of determining the mass of multiply charged electrospray ions generated from samples of macromolecules in the megadalton (MDa) size range. The instrument utilizes a sensitive amplifier which can detect the charge on a single ion as it passes through a tube detector. A velocity measurement of an ion with known electrostatic energy provides the ion's mass-to-charge ratio. Simultaneous detection of the ion charge permits a mass assignment to be made for each ion. Electrospray ions of DNA and polymer molecules with masses greater than 1 x 10(6) Da and charge numbers (z) in excess of 425 e(-) are readily detected in this mass spectrometer. The weights of small particles were also measured. The on-axis single-ion detection configuration provides a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.     

Formation of lithiated adducts of glycerophosphocholine lipids facilitates their identification by electrospray ionization tandem mass spectrometry

Electrospray ionization (ESI) tandem mass spectrometry (MS) has simplified analysis of phospholipid mixtures, and, in negative ion mode, permits structural identification of picomole amounts of phospholipid species. Collisionally activated dissociation (CAD) of phospholipid anions yields negative ion tandem mass spectra that contain fragment ions representing the fatty acid substituents as carboxylate anions. Glycerophosphocholine (GPC) lipids contain a quaternary nitrogen moiety and more readily form cationic adducts than anionic species, and positive ion tandem mass spectra of protonated GPC species contain no abundant ions that identify fatty acid substituents. We report here that lithiated adducts of GPC species are readily formed by adding lithium hydroxide to the solution in which phospholipid mixtures are infused into the ESI source. CAD of [MLi+] ions of GPC species yields tandem mass spectra that contain prominent ions representing losses of the fatty acid substituents. These ions and their relative abundances can be used to assign the identities and positions of the fatty acid substituents of GPC species. Tandem mass spectrometric scans monitoring neutral losses of the head-group or of fatty acid substituents from lithiated adducts can be used to identify GPC species in tissue phospholipid mixtures. Similar scans monitoring parents of specific product ions can also be used to identify the fatty acid substituents of GPC species, and this facilitates identification of distinct isobaric contributors to ions observed in the ESI/MS total ion current.     

Simultaneous assessment of conformation and aggregation of beta-amyloid peptide using electrospray ionization mass spectrometry

Electrospray ionization mass spectrometry was used to study conformation and aggregation of the synthetic beta-amyloid peptide, residues 1-40 (betaA4), as a function of concentration and sample aging. All mass spectra showed a major envelope of peaks corresponding to charge states of 7-3 of the monomeric form of betaA4. In addition, weaker envelopes of peaks corresponding to charge states of dimeric, trimeric, and tetrameric betaA4 species were seen under gentle ionization conditions. The average charge state of the envelope associated with the monomeric form decreased by ca. 0.5 z as samples were aged, indicating that the relatively open form (likely random coil) of the peptide was modified into the more compact form (likely beta-sheet) as a function of sample aging. The aggregate forms became weaker and ultimately were absent both in the more dilute solutions and in aged aliquots of the concentrated sample. These aggregates were interpreted as assemblies of the random coil form. We interpret our inability to see an ion envelope that can be associated with aggregates of the beta-sheet form to be a consequence of the presumed very compact nature of this form. A model for the formation of betaA4 fibrils is proposed and discussed.