Evolutionary patterns from mass originations and mass extinctions

The Fossil Record 2 database gives a stratigraphic range of most known animal and plant families. We have used it to plot the number of families extant through time and argue for an exponential fit, rather than a logistic one, on the basis of power spectra of the residuals from the exponential. The times of origins and extinctions, when plotted for all families of marine and terrestrial organisms over the last 600 Myr, reveal different origination and extinction peaks. This suggests that patterns of biological evolution are driven by its own internal dynamics as well as responding to upsets from external causes. Spectral analysis shows that the residuals from the exponential model of the marine system are more consistent with 1/f noise suggesting that self-organized criticality phenomena may be involved.     

Scaling of skeletal mass to body mass in fishes

The few available observations are consistent with the supposition that the relative weightlessness of fishes leads to isometric scaling of skeletal mass to body mass. To explore further this pattern we studied scaling in ontogeny with freshwater tilapia, Oreochromis nilotica, and in phylogeny with adult coral reef fishes. Body mass and skeletal mass were measured for freshly caught fishes. Data were transformed to logarithms and fitted to a power function with least-square linear regression. Whereas slope for all O. nilotica combined was consistent with isometry (b = 1.00; 95% CI = 0.02), slopes calculated separately for juveniles (b = 1.16; CI = 0.07) and adults (b = 1.10; CI = 0.07) indicated positive allometric scaling of the skeleton during ontogeny. The scaling pattern was isometric for a multispecies sample of perciform fishes from coral reefs (b = 0.82; CI = 0.21). However, the single perciform species with the largest number of individuals in the sample, Epinephelus guttatus, was positively allometric (b = 1.13; CI = 0.12), whereas the tetraodontiform, Balistes vetula, was isometric (b = 1.05; CI = 0.12). Instead of leading to isometry, weightlessness may increase the range of possibilities for the scaling of skeleton mass to body mass in fishes compared to terrestrial vertebrates. The scaling of the skeleton in fishes may be related to foraging style and manner of locomotion in water rather than be driven by the need to resist gravity. © 1996 Wiley-Liss, Inc.     

Accurate mass analysis of phosphoramidites by electrospray mass spectrometry

A method of accurate mass determination of phosphoramidites is described. The commonly used methanol/water/acid system was replaced by LiCl-containing acetonitrile and the concentrations of LiCl, poly(ethylene glycol), and phosphoramidite samples were optimized.     

Numerical bias estimation for mass spectrometric mass isotopomer analysis

Mass spectrometric (MS) isotopomer analysis has become a standard tool for investigating biological systems using stable isotopes. In particular, metabolic flux analysis uses mass isotopomers of metabolic products typically formed from ¹³C-labeled substrates to quantitate intracellular pathway fluxes. In the current work, we describe a model-driven method of numerical bias estimation regarding MS isotopomer analysis. Correct bias estimation is crucial for measuring statistical qualities of measurements and obtaining reliable fluxes. The model we developed for bias estimation corrects a priori unknown systematic errors unique for each individual mass isotopomer peak. For validation, we carried out both computational simulations and experimental measurements. From stochastic simulations, it was observed that carbon mass isotopomer distributions and measurement noise can be determined much more precisely only if signals are corrected for possible systematic errors. By removing the estimated background signals, the residuals resulting from experimental measurement and model expectation became consistent with normality, experimental variability was reduced, and data consistency was improved. The method is useful for obtaining systematic error-free data from ¹³C tracer experiments and can also be extended to other stable isotopes. As a result, the reliability of metabolic fluxes that are typically computed from mass isotopomer measurements is increased.     

Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap

Mass accuracy is a key parameter of mass spectrometric performance. TOF instruments can reach low parts per million, and FT-ICR instruments are capable of even greater accuracy provided ion numbers are well controlled. Here we demonstrate sub-ppm mass accuracy on a linear ion trap coupled via a radio frequency-only storage trap (C-trap) to the orbitrap mass spectrometer (LTQ Orbitrap). Prior to acquisition of a spectrum, a background ion originating from ambient air is first transferred to the C-trap. Ions forming the MS or MS(n) spectrum are then added to this species, and all ions are injected into the orbitrap for analysis. Real time recalibration on the "lock mass" by corrections of mass shift removes mass error associated with calibration of the mass scale. The remaining mass error is mainly due to imperfect peaks caused by weak signals and is addressed by averaging the mass measurement over the LC peak, weighted by signal intensity. For peptide database searches in proteomics, we introduce a variable mass tolerance and achieve average absolute mass deviations of 0.48 ppm (standard deviation 0.38 ppm) and maximal deviations of less than 2 ppm. For tandem mass spectra we demonstrate similarly high mass accuracy and discuss its impact on database searching. High and routine mass accuracy in a compact instrument will dramatically improve certainty of peptide and small molecule identification.     

Enhanced peptide mass fingerprinting through high mass accuracy: Exclusion of non-peptide signals based on residual mass

Peptide mass fingerprinting (PMF) is among the principle methods of contemporary proteomic analysis. While PMF is routinely practiced in many laboratories, the complexity of protein tryptic digests is such that PMF based on unrefined mass spectrometric peak lists is often inconclusive. A number of data processing strategies have thus been designed to improve the quality of PMF peak lists, and the development of increasingly elaborate tools for PMF data reduction remains an active area of research. In this report, a novel and direct means of PMF peak list enhancement is suggested. Since the monoisotopic mass of a peptide must fall within a predictable range of residual values, PMF peak lists can in principle be relieved of many non-peptide signals solely on the basis of accurately determined monoisotopic mass. The calculations involved are relatively simple, making implementation of this scheme computationally facile. When this procedure for peak list processing was used, the large number of unassigned masses typical of PMF peak lists was considerably attenuated. As a result, protein identifications could be made with greater confidence and improved discrimination as compared to PMF queries submitted with raw peak lists. Importantly, this scheme for removal of non-peptide masses was found to conserve peptides bearing various post-translational and artificial modifications. All PMF experiments discussed here were performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), which provided the high mass resolution and high mass accuracy essential for this application. Previously reported equations relating the nominal peptide mass to the permissible range of fractional peptide masses were slightly modified for this application, and these adjustments have been illustrated in detail. The role of mass accuracy in application of this scheme has also been explored.     

From mass customization to mass personalization: a strategic transformation

Business and operations strategists have long sought to formulate strategies that would serve profitably for a market of one. Two decades after its conception, there is growing evidence that mass customization strategy is transforming into a mass personalization strategy, making the market of one a reality, at least in select industries. The degree of transformation of a company depends on the extent to which its product is soft, i.e., can be produced electronically. Thus, at the lower end of the personalization spectrum are manufacturing companies engaged in producing hard, configurable products, while on the high end of the spectrum are service companies whose product can be totally configured and delivered electronically. The underlying factors that are enabling this transformation, in our view, are: (1) development of information technologies such as peer to peer (P2P), business to consumer (B2C), and Web 2.0, (2) near-universal availability of the Internet, (3) customer willingness and preparedness to be integrated into the process of product co-design and co-creation, (4) modern manufacturing systems, such as flexible manufacturing and, of course, (5) mass customization tools such as modularity and delayed differentiation, which help reduce manufacturing cost and cycle times and (6) deployment of customer-satisfaction-specific software called customer relationship management (CRM) to engender customer retention. Due to the importance and strategic success of affordable personalization, this issue is dedicated to that theme. The articles included in this issue would, I believe, serve as significant decision support mechanisms for companies pursuing a mass customization and personalization strategy. In addition to providing a brief perspective on articles included in this issue, we also summarize the state of the art of mass customization research.     

On mass behavior

In imitative behavior, as studied previously by N. Rashevsky (Mathematical Biology of Sociol Behavior, Chapter XIII, The University of Chicago Press, 1950), the reason for the majority of a society to accept a particular behavior is based on purely voluntary action (band-wagon effect). In the present paper effects of coercion of the majority by a small minority group which poses the means for coercion, are studied. More general types of equations are thus obtained and threshold effects found, which bear a resemblance to some such effects studied previously.     

Charge variant native mass spectrometry benefits mass precision and dynamic range of monoclonal antibody intact mass analysis

ABSTRACT

The preponderance and diversity of charge variants in therapeutic monoclonal antibodies has implications for antibody efficacy and degradation. Understanding the extent and impact of minor antibody variants is of great interest, and it is also a critical regulatory requirement. Traditionally, a combination of approaches is used to characterize antibody charge heterogeneity, including ion exchange chromatography and independent mass spectrometric variant site mapping after proteolytic digestion. Here, we describe charge variant native mass spectrometry (CVMS), an integrated native ion exchange mass spectrometry-based charge variant analytical approach that delivers detailed molecular information in a single, semi-automated analysis. We utilized pure volatile salt mobile phases over a pH gradient that effectively separated variants based on minimal differences in isoelectric point. Characterization of variants such as deamidation, which are traditionally unattainable by intact mass due to their minimal molecular weight differences, were measured unambiguously by mass and retention time to allow confident MS1 identification. We demonstrate that efficient chromatographic separation allows introduction of the purified forms of the charge variant isoforms into the Orbitrap mass spectrometer. Our CVMS method allows confident assignment of intact monoclonal antibody isoforms of similar mass and relative abundance measurements across three orders of magnitude dynamic range.     

Peptide mass fingerprinting

Peptide mass fingerprinting by MALDI-MS and sequencing by tandem mass spectrometry have evolved into the major methods for identification of proteins following separation by two-dimensional gel electrophoresis, SDS-PAGE or liquid chromatography. One main technological goal of proteome analyses beside high sensitivity and automation was the comprehensive analysis of proteins. Therefore, the protein species level with the essential information on co- and post-translational modifications must be achieved. The power of peptide mass fingerprinting for protein identification was described here, as exemplified by the identification of protein species with high molecular masses (spectrin alpha and beta), low molecular masses (elongation factor EF-TU fragments), splice variants (alpha A crystallin), aggregates with disulfide bridges (alkylhydroperoxide reductase), and phosphorylated proteins (heat shock protein 27). Helpful tools for these analyses were the use of the minimal protein identifier concept and the software program MS-Screener to remove mass peaks assignable to contaminants and neighbor spots.     

MALDI-TOF mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) has developed during the past decade into a versatile tool for biopolymer analysis. The aim of this review is to summarize this development and outline the applications, which have been enabled for routine use in the field of nucleic acid analysis. These include the anlaysis of mutations, the resequencing of amplicons with a known reference sequence, and the quantitative analysis of gene expression and allelic frequencies in complex DNA mixtures.     

Correlation between skeletal calcium mass and muscle mass in man.

The measurements of total body potassium (TBK) and calcium (TBCa) were made on 317 subjects by the techniques of whole-body counting and total-body neutron activation analysis (TBNAA), respectively. The TBK/TBCa ratios are constant for normals over the age range studied. The males have more cellular mass (TBK) per unit skeletal mass (TBCa) than the females, as indicated by their respective TBK/TBCa ratios, 0.122 +/- 0.008 (1 SD), and 0.100 +/- 0.007 (1 SD). In general, patients with various metabolic disorders tend to follow the physiological trend found in the normals. In a number of metabolic disorders, the loss of TBK was usually approximately 60% of that of the TBCa when expressed in terms of the predicted normal values. This suggests that the mechanism causing the loss of calcium in physiological and altered metabolic states simultaneously involves both the skeleton and its associated musculature.     

成年人脂肪体重、去脂体重和肺通气功能的关系

本文旨在研究分析成年人去脂体重(fat free mass,FFM)、脂肪体重(fat mass,FM)和肺通气功能的关系。随机抽取黑龙江省部分地区19~81岁健康成年人群1307人(男性372人,女性935人),测量身高、体重,采用身体成分仪和肺功能仪分别检测FFM、FM和肺通气功能,并采用Pearson相关分析、独立样本t检验和多元逐步回归等统计学方法分析FFM、FM和肺通气功能的关系。结果显示,无论性别,年龄均与脂肪体重指数(FM index,FMI)呈正相关(P0.001),去脂体重指数(FFM index,FFMI)和用力肺活量(forced vital capacity,FVC)、用力呼气一秒量(forced expiratory volume in one second,FEV1)、最高呼气流量(peak expiratory flow,PEF)、用力呼出25%肺活量时呼气流量(forced expiratory flow at25%of forcedvital capacity,FEF25%)均呈正相关(P0.01),FMI和FVC、FEV1、FEF75%呈负相关(P0.05)。男性FMI和最大呼气中段流量(maximal mid-expiratory flow,MMEF)呈负相关(P0.05)。无论性别,FFMI对于FVC作用大于FMI,而对于FEV1,男性FMI作用大于FFMI,女性则反之。无论性别,FFMI升高,PEF和FEF25%也升高,而FMI对二者无作用。无论性别,FMI升高,FEF75%降低,而FFMI对其无作用。FMI升高,男性MMEF降低,女性无明显改变。本研究结果表明,FFM和FM均是影响肺通气功能的独立因素,反映骨骼肌力的FFM与肺通气功能呈正相关,FM与肺通气功能呈负相关。FFM和FM对肺通气功能作用大小存在差别。     

Waist circumference adjusted for body mass index and intra-abdominal fat mass

Background

The association between waist circumference (WC) and mortality is particularly strong and direct when adjusted for body mass index (BMI). One conceivable explanation for this association is that WC adjusted for BMI is a better predictor of the presumably most harmful intra-abdominal fat mass (IAFM) than WC alone. We studied the prediction of abdominal subcutaneous fat mass (ASFM) and IAFM by WC alone and by addition of BMI as an explanatory factor.

Methodology/Principal Findings

WC, BMI and magnetic resonance imaging data from 742 men and women who participated in clinical studies in Canada and Finland were pooled. Total adjusted squared multiple correlation coefficients (R²) of ASFM and IAFM were calculated from multiple linear regression models with WC and BMI as explanatory variables. Mean BMI and WC of the participants in the pooled sample were 30 kg/m² and 102 cm, respectively. WC explained 29% of the variance in ASFM and 51% of the variance in IAFM. Addition of BMI to WC added 28% to the variance explained in ASFM, but only 1% to the variance explained in IAFM. Results in subgroups stratified by study center, sex, age, obesity level and type 2 diabetes status were not systematically different.

Conclusion/Significance

The prediction of IAFM by WC is not improved by addition of BMI.     

Analysis of polyunsaturated aminophospholipid molecular species using isotope-tagged derivatives and tandem mass spectrometry/mass spectrometry/mass spectrometry

When aminophospholipids with only saturated and monounsaturated fatty acids esterified to the glycerol backbone were labeled with isotopically enriched N-methylpiperazine acetic acid N-hydroxysuccinimide ester reagents, it was found that they could be readily detected as N-methylpiperazine-amide-tagged aminophospholipids using a precursor scan of the stable isotope reporter ion (m/z 114-117) formed by tandem mass spectrometry/mass spectrometry. However, it was found in the current study that these precursor ion scans are not useful in determining the changes of aminophospholipids with polyunsaturated fatty acids (PUFAs) esterified to the glycerol backbone due to the presence of interfering ions in the reporter ion region. Therefore, a method was developed using tandem mass spectrometry/mass spectrometry/mass spectrometry (MS(3)) to obtain reporter ion ratios that were not distorted by interfering ions present in the collision-induced dissociation spectra of nontagged aminophospholipids with PUFAs. This new MS(3) method for N-methylpiperazine- amide-tagged aminophospholipids was used to examine the fate of diacyl, ether, or plasmalogen glycerophosphoethanolamine (GPEtn) species after exposure of human polymorphonuclear leukocytes to A23187 and granulocyte macrophage-colony-stimulating factor/formyl-methionyl-leucyl-phenylalanine stimuli, which can induce eicosanoid biosynthesis, to follow those GPEtn molecular species which were the source of arachidonic acid released. Upon stimulation of the human polymorphonuclear leukocyte, it was found that the abundant arachidonoyl GPEtn plasmalogen molecular species were uniquely reduced in relative content compared to ether or diacyl species and this subclass of GPEtn may be a source of the arachidonic acid converted to leukotrienes by the 5-lipoxygenase pathway activated in this cell.     

A platform for accurate mass and time analyses of mass spectrometry data

We describe an integrated suite of algorithms and software for general accurate mass and time (AMT) tagging data analysis of mass spectrometry data. The AMT approach combines identifications from liquid chromatography (LC) tandem mass spectrometry (MS/MS) data with peptide accurate mass and retention time locations from high-resolution LC-MS data. Our workflow includes the traditional AMT approach, in which MS/MS identifications are located in external databases, as well as methods based on more recent hybrid instruments such as the LTQ-FT or Orbitrap, where MS/MS identifications are embedded with the MS data. We demonstrate our AMT workflow's utility for general data synthesis by combining data from two dissimilar biospecimens. Specifically, we demonstrate its use relevant to serum biomarker discovery by identifying which peptides sequenced by MS/MS analysis of tumor tissue may also be present in the plasma of tumor-bearing and control mice. The analysis workflow, referred to as msInspect/AMT, extends and combines existing open-source platforms for LC-MS/MS (CPAS) and LC-MS (msInspect) data analysis and is available in an unrestricted open-source distribution.