Periodicity of monoisotopic mass isomers and isobars in proteomics

We report trends in the theoretically derived number of compositionally distinct peptides (i.e., peptides made up of different amino acid residues) up to a nominal mass of 1000. A total of 21 amino acid residues commonly found in proteomics studies are included in this study, 19 natural, nonisomeric amino acid residues as well as oxidated methione and acetamidated cysteine. The number of possibilities is found to increase in an exponential fashion with increasing nominal mass, and the data show a periodic oscillation that starts at mass ~200 and continues throughout to 1000. Note that similar effects are reported in the companion article on fragment ions from electron capture/transfer dissociation (ECD/ETD) (Mao et al. Anal. Chem.2011, DOI: 10.1021/ac201619t). The spacing of this oscillation is ~15 mass units at lower masses and ~14 mass units at higher nominal masses. This correlates with the most common mass differences between the amino acid building blocks. In other words, some mass differences are more common than others, thus determining the periodicity in this data. From an analytical point of view, nominal masses with a larger number of compositionally distinct peptides include a substantial number of isomers, which cannot be separated based on mass. Consequently, even ultrahigh mass accuracy (i.e., 0.5 ppm) does not lead to a substantially enhanced rate of identification. Conversely, for adjacent nominal masses with a lower number of isomers, moderately accurate mass (i.e., 10 ppm) gives a higher degree of certainty in identification. These effects are limited to the mass range between 200 and 500 Da. At higher masses, the percentage of uniquely identified peptides drops off to close to zero, independent of nominal mass, due the inherently high number of isomers. While the exact number of isobars/isomers at each nominal mass depends on the amino acid building blocks that are considered, the periodicity in the data is found to be remarkably robust; for instance, inclusion of phosphorylated residues barely affects the pattern at lower masses (i.e., <500 Da).     

三维焊缝形貌信息的变基准测量数据处理方法

为了实现大型航空航天薄壁结构件的精密激光焊接,在研制开发＂5＋2＂轴激光焊接测量系统的基础上,提出了一种变基准测量数据处理方法,通过齐次坐标变换,将表达在局部测量基准下的三维焊缝形貌信息转换到统一的机床基准下,建立了三维焊缝的几何模型,并对机床几何误差进行了分析与补偿。以某型号航空航天结构模拟件为例,通过在线测量、数据处理、几何建模以及编程加工进行验证,结果表明该方法能够满足实际加工的要求。     

Differentiation of isomers by wavelength-tunable infrared multiple-photon dissociation-mass spectrometry: application to glucose-containing disaccharides

Variation in the wavelength of irradiation in infrared multiple-photon dissociation (IR-MPD) of lithium-tagged glucose-containing disaccharide ions (1-2-, 1-3-, 1-4-, and 1-6-linked isomers of both anomeric configurations) resulted in marked differences in their mass spectral fragmentation patterns. Two-dimensional plots of the fragment yield versus infrared wavelength for each mass spectral product ion were unique for each isomer and can be considered a spectral fingerprint. Individual product ions or diagnostic ratios of key product ions can be optimized at specific IR wavelengths. The technique permits both linkage position and anomeric configuration to be assigned. The ratio of the fragments derived by cleavage at the glycosidic bond (m/z 169/187) is much enhanced for beta-anomers compared to alpha-anomers. Differences in the diagnostic product ions 169 and 187 were largest in the range of 9.0-9.4 microm, where the maximum dissociation yield was observed. Conversely, at 10.6 microm, the wavelength of nontunable CO2 lasers that accompany commercial Fourier transform ion cyclotron resonance mass spectrometers, the dissociation yield was poor and anomeric differentiation was not possible. In contrast to previous studies by collision-induced dissociation, the trends in dissociation behavior between anomers using IR-MPD are significant and allow simple diagnostic rules to be established. By depositing energy into these isobaric ions via narrow-band IR excitation, the resulting internal energy can be finely controlled, thereby obtaining high reproducibility in dissociation patterns. Given the multidimensionality of variable-wavelength IR-MPD of lithiated disaccharides, it is expected that this approach can overcome some of the current limitations in isomer differentiation.     

Anti-sulphatide antibodies in peripheral neuropathy

A study was carried out on 135 patients with chronic idiopathic neuropathy (63), neuropathy associated with monoclonal gammopathy (51, including eight with anti-MAG antibody activity) and the Guillain-Barré syndrome (GBS) (21). Serum IgM, IgG and IgA anti-sulphatide antibody titres were compared with titres in 304 patients with other neurological or immunological diseases and in 50 normal subjects. Titres were presented a) as the highest serum dilution at which reactivity could be detected, and b) in the linear region of the optical density curve. A substantial number of patients with neurological or immunological diseases had higher titres than normal subjects. Compared with normal and disease controls, five patients with neuropathy associated with IgMk monoclonal gammopathy had raised titres of IgM anti-sulphatide antibodies and one patient with GBS had raised IgM, IgG and IgA anti-sulphatide antibodies in the acute phase of the disease. Two patients had a predominantly axonal sensory neuropathy with presenting symptoms of painful paresthesiae and minimal neurological deficit. Three patients had a predominantly demyelinating sensorimotor neuropathy associated with anti-MAG antibody activity. The patient with GBS had extensive sensory loss and antibody titres returned to normal within three weeks. Raised titres of anti-sulphatide antibodies occurred in several types of neuropathy, but all had some degree of sensory impairment and associated immunological abnormality.     

Bone marrow monocyte/macrophages are an early cellular target of pathogenic and nonpathogenic isolates of simian immunodeficiency virus (SIVmac) in rhesus macaques

BACKGROUND: Hematopoietic abnormalities are a common complication of human immunodeficiency virus infection in humans. However, the pathogenesis of these abnormalities remains unclear. Simian immunodeficiency virus (SIV) infection of rhesus macaques is a well-recognized animal model for acquired immunodeficiency syndrome. Our previous studies have determined that in early SIV infection, rhesus macaques develop peripheral blood and bone marrow pathologic changes within the first 14 days after intravenous inoculation. Further investigations were initiated to determine the onset of bone marrow viral infection and the identity of in vivo viral cellular targets in bone marrow during the primary phase of infection in macaques infected with three different strains of SIVmac. EXPERIMENTAL DESIGN: Rhesus macaques experimentally infected with pathogenic uncloned biologic SIVmac, molecularly cloned pathogenic SIVmac-239, or nonpathogenic SIVmac-1A11 were studied at 3, 7, and 14 days postinoculation. Bone marrow samples taken at necropsy were examined to identify early in vivo cellular targets of SIVmac in bone marrow and to correlate hematopathologic lesions with viral infection. In the first 2 weeks after intravenous inoculation, cellular targets of viral infection were identified by a combined in situ hybridization/immunohistochemical technique; changes in bone marrow monocyte/macrophage and CD3+ T lymphocyte populations were evaluated by immunohistochemical techniques. RESULTS: SIV-infected monocyte/macrophages were detected on days 3, 7, and 14 days postinoculation in bone marrow of all monkeys regardless of the viral isolate, whereas only a few SIV-infected CD3+ T lymphocytes were detected in 5 of 18 monkeys. The bone marrow morphologic changes associated with acute SIV infection included macrophage hyperplasia and apparent macrophage activation, diminution of bone marrow T lymphocytes, appearance of lymphoid aggregates, and myeloid and megakaryocytic hyperplasia. CONCLUSIONS: We conclude that bone marrow monocyte/macrophages are an important early cellular target in SIV infection regardless of viral pathogenicity and in vitro cellular tropism. SIV-infected bone marrow monocyte/macrophages may play a key role in the pathogenesis of bone marrow lesions and further dissemination and persistence of virus infection.     

Quantitative study on the effect of osthole on proximal tibiae in ovariectomized (OVX) rats

OBJECTIVE: To determine if a correlation exists between the level of maternal serum alpha-fetoprotein (MSAFP) elevation and the rate of adverse pregnancy outcome, to examine the timing of pregnancies ending in fetal or neonatal death, and to develop a protocol for antepartum surveillance in an effort to prevent these adverse outcomes. STUDY DESIGN: Singleton pregnancies with a single second-trimester elevated MSAFP > or = 2.0 multiples of the median (MoM) were eligible if a targeted ultrasound evaluation (< 24 weeks) was in agreement with the dates and no fetoplacental anomaly was detected. Three groups were established based on the second-trimester MSAFP elevation: 2.0-2.49, 2.5-2.99 and > or = 3.0 MoM. RESULTS: Among the 383 patients enrolled, delivery data were available on 333 infants. Stratified by MSAFP elevations of 2.0-2.49, 2.5-2.99 and > or = 3.0 MoM, the rates of adverse pregnancy outcome were: (1) preterm birth: 14.3%, 15.6%, 20.3%; (2) small for gestational age at birth: 7.4%, 11.1%, 22.2%; and (3) perinatal deaths (neonatal and fetal): 2.6%, 3.3%, 5.6%. Seven pregnancy losses (three neonatal and four fetal deaths) occurred prior to 28 weeks. Of these seven, six fetuses exhibited intrauterine growth retardation by 23-26 weeks' gestation, and five of six were associated with MSAFP levels > or = 2.5 MoM. Four losses (two neonatal and two fetal deaths) occurred after 28 weeks. Of these, three involved structurally normal infants with normal growth who died after 34 weeks. All three of these pregnancies exhibited MSAFP elevations < 2.5 MoM. CONCLUSION: In pregnancies with an unexplained elevated second-trimester MSAFP, the rate of adverse pregnancy outcomes is increased with higher elevations. Any proposed program to improve pregnancy outcome in patients with unexplained MSAFP elevations must include efforts aimed at preventing preterm delivery, repeat ultrasound at 24-26 weeks to rule out early-onset intrauterine growth retardation in pregnancies with elevations > or = 2.5 MoM and fetal biophysical monitoring, even in normally grown fetuses, instituted at 32 weeks to detect fetuses at risk for intrauterine death.