A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies

We report the design and first applications of a tandem mass spectrometer (a quadrupole time-of-flight mass spectrometer) optimized for the transmission and analysis of large macromolecular assemblies. Careful control of the pressure gradient in the different pumping stages of the instrument has been found to be essential for the detection of macromolecular particles. Such assemblies are, however, difficult to analyze by tandem-MS approaches, because they give rise to signals above m/z 3,000-4,000, the limit for commercial quadrupoles. By reducing the frequency of the quadrupole to 300 kHz and using it as a narrow-band mass filter, we show that it is possible to isolate ions from a single peak at m/z 22,000 in a window as narrow as 22 m/z units. Using cesium iodide cluster signals, we show that the mass range in the time-of-flight (TOF) analyzer extends beyond m/z 90,000, in theory to more than m/z 150,000. We also demonstrate that the resolution of the instrument is greater than 3,000 at m/z 44,500. Tandem-MS capabilities are illustrated by separating components from heterooligomeric assemblies formed between tetrameric transthyretin, thyroxine, retinol-binding protein, and retinol. Isolation of a single charge state at m/z 5,340 in the quadrupole and subsequent collision-induced dissociation (CID) in the gas-filled collision cell leads to the formation of ions from individual subunits and subcomplexes, identified by their mass and charge in the TOF analyzer.     

Deficits on the continuous performance test within the schizophrenia spectrum and the mediating effects of family history of schizophrenia.

Individuals with schizophrenia spectrum personality disorders (SSPD) and schizophrenia show similar cognitive impairments. The authors examined the contributions of SSPD symptoms and familial risk for schizophrenia to impairments on the Continuous Performance Test-Identical Pairs Version. Participants included 103 schizophrenia patients, 66 first-degree relatives (29 SSPD), and 103 community controls (26 SSPD) screened for family history of psychosis. Patients and SSPD relatives performed significantly worse than non-SSPD relatives and SSPD and non-SSPD community controls. No differences in performance were observed among non-SSPD relatives and SSPD and non-SSPD community controls. Results suggest a continuum in which risk for schizophrenia-related cognitive impairments is highest among patients and SSPD relatives, intermediate among non-SSPD relatives, and lowest among SSPD and non-SSPD community controls. Results suggest that SSPD in the absence of a family history of psychosis may be a phenocopy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

We have always been transgenic

This dialogue concerns the nature of ethical responsibility in contemporary art practice, and its relation to questions of creativity; the role of writing in shaping the perception of transgenic art and related practices; and the problems that may be associated with trusting artists to act with integrity in the unchartered waters of their enthusiastic engagement with genetic technologies.     

Visualisation of extensive water ribbons and networks in a DNA minor-groove drug complex

The crystal structure is reported of a complex between an ethyl derivative of the minor-groove drug furamidine and the dodecanucleotide duplex d(CGCGAATTCGCG)2, which has been refined to 1.85 A resolution and an R factor of 16.6% for data collected at -173 degreesC. An exceptionally large number (220) of water molecules have been located. The majority of these occur in the first coordination shell of solvation. There are extensive networks of connected waters, both in the major and minor grooves. In particular, there are 21 water molecules associated with the minor-groove drug, via hydrogen bonds from the four charged nitrogen atoms. One cluster of four waters is situated in the groove itself; the majority are on the outer edge of the groove, and serve to bridge between the outward-directed drug nitrogen atoms and backbone phosphate oxygen atoms. These bridges are both intra- and inter-strand, with the net effect that the outer edge of the drug molecule is covered by ribbons of water molecules.     

Computational complexity and constraint logic programming languages

We give a complexity analysis of a variety of languages across the spectrum of the CLP scheme. By varying the logic and memory management, the role of the constraints and the role of the logic can be measured. The analysis clarifies the relation between linear/integer programming and constraint logic programming. We also determine how the power of constraints can easily lead to undecidable queries in Datalog languages with constraints. This work is motivated in large part by the problems of efficient implementation of CLP languages and the concomitant need for low level constraint languages.Research partially supported by PSC-CUNY Grant 669287.Research partially supported by NSF Grant IRI-8902511.     

Traumatic brain injury and memory: The role of hippocampal atrophy.

In traumatically brain-injured (TBI) patients (n?=?83), memory performance was examined on the Warrington Recognition Memory Test, Rey-Osterrieth Complex Figure, and the Logical Memory and Visual Reproduction subtests of the Wechsler Memory Scale-Revised in relationship to time postinjury and structural changes based on MRI volumetry, including hippocampus volume. Significant trauma-induced changes were observed, including hippocampal atrophy. Structure-function relationships generally became significant only after 90 days postinjury. Memory tended to relate more to the degree of hippocampal atrophy, particularly left hippocampus, than to nonspecific indicators such as the temporal horns or the ventricle-to-brain ratio. A stronger relationship with left versus right hippocampus was evident for measures of verbal and supposedly nonverbal memory. These results are discussed with regard to the role the hippocampus may play in a neural system of memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A mucosal IgA response, but no systemic antibody response, is evoked by intranasal immunisation of dogs with Echinococcus granulosus surface antigens iscoms

Current understanding of the pathogenesis of rheumatoid arthritis has provided evidence that therapeutic benefit can be achieved by using antagonists targeted to the inflammatory cytokines involved, mainly tumour necrosis factor-alpha and interleukin-1. Gene delivery of antagonists, which can inhibit the production or action of these cytokines and other mediators, has been achieved in experimental animal models. This new method of delivery can produce therapeutic effects at lower concentrations and in a local environment, overcoming the adverse effects that often accompany protein therapy. However, several technological and biological restraints preclude the immediate adaptation of this method to human treatment. Based on the experimental evidence, possible target therapeutic genes, cell types and vector systems that could be used are discussed in this article.     

Neonatal exposure to cocaine enhances the reward-potentiating properties of the drug in young adult animals.

Either cocaine (20 mg/kg) or saline vehicle was administered to rat pups once daily on postnatal days 1–8. The enhancement of braid stimulation reward (BSR) by acute administration of cocaine (2.5, 5, and 10 mg/kg ip) was assessed in adult offspring (70–90 days of age) using a rate-frequency curve-shift paradigm. Acute administration of cocaine produced orderly dose-related shifts of the rate-frequency function toward lower frequencies in all groups indicating a reward-enhancing effect of the drug on BSR. However, offspring neonatally exposed to cocaine displayed a greater drug-induced potentiation of BSR. Of particular note, the small but significant enhancement of the reward-potentiating properties of cocaine was more pronounced in female offspring neonatally exposed to the drug. These findings indicate that the rewarding properties of cocaine were altered by neonatal exposure to the drug in a sexually dimorphic fashion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)